Thousands of junior doctors have begun the first all-out strike in the history of the NHS after the Health Secretary said the Government would not be "blackmailed" into dropping its manifesto pledge for a seven-day health service.
Jeremy Hunt appealed directly to medics on Monday not to withdraw emergency cover, which he said had particular risks for A&E departments, maternity and intensive care.
The impasse between the Government and the British Medical Association (BMA) prompted the industrial action, from 8am to 5pm on Tuesday and again on Wednesday.
It is the first time services such as A&E, maternity and intensive care have been affected during the dispute over a new contract.
Speaking on BBC Breakfast, Mr Hunt accused union leaders of trying to "blackmail" the Government with strike action.
He said he could only call a halt to the action "by abandoning a manifesto promise that the British people voted on" at last year's general election.
The Health Secretary said: "It was the first page of our manifesto that we'd have a seven-day NHS.
"I don't think any union has the right to blackmail the Government, to force the Government to abandon a manifesto promise that the British people have voted on."
Despite an intense three days of letters back and forth and a phone call between Mr Hunt and the head of the BMA on Monday, no agreement on a way forward has been reached.
Mr Hunt said he was motivated by a desire to improve weekend services in the NHS and told MPs that "no trade union" had the right to veto a Government manifesto commitment to do so.
He said the disruption over the next two days is "unprecedented" but the NHS has made "exhaustive efforts" to ensure patient safety.
He said: "No trade union has the right to veto a manifesto promise voted for by the British people.
"We are proud of the NHS as one of our greatest institutions but we must turn that pride into actions and a seven-day service will help us turn the NHS into one of the highest quality healthcare systems in the world.
"I wish to appeal directly to all junior doctors not to withdraw emergency cover, which creates particular risks for A&Es, maternity units and intensive care units."
Mr Hunt said the NHS was "busting a gut to keep the public safe".
An Ipsos Mori poll for BBC News has found 57% support the doctors' cause while a quarter oppose it.
The majority still think the Government is most at fault for the dispute - but a rising number think the Government and doctors are equally to blame.
Public support for the all-out strike, where no emergency care is provided, appears to be higher than in January.
While 57% support the current walkout, the figure supporting a full strike was 44% at the start of the year, the survey of 861 adults showed.
More than 125,000 appointments and operations have been cancelled and will need to be rearranged across England's hospitals as a result of the latest dispute.
The BMA has defended the walkout, repeating its stance that it would have called off the strike if Mr Hunt agreed to lift his threat to impose the contract.
The head of the BMA, Mark Porter, told the BBC Radio 4 Today programme on Monday that the Government had "distorted" weekend death statistics, and stressed that emergency cover would be provided by consultants during the strike.
Responding to Mr Hunt's claim that lives were being put at risk by the strike, he added: "The Health Secretary is trying to find some way to throw mud at the junior doctors of this country who have been providing weekend and night emergency cover since the NHS started."
Earlier on Monday, more than a dozen presidents of royal colleges and faculties urged Prime Minister David Cameron to step in "at the 11th hour" to break the stalemate.
Labour leader Jeremy Corbyn said Mr Hunt should "back off ", adding: "We must stand up and defend the NHS."
He also asked if there was a "deeper agenda" to reduce the efficiency of the NHS while promoting private industry.
Mr Hunt denied the Government had been looking for a battle with public sector unions and accused "elements" within the BMA of refusing to reach any compromise agreement.
"The last thing we are doing is itching for a fight," he told the BBC Radio 4 Today programme.
"Insofar as it is a political strike, I do think there are some elements - not the majority and certainly not the majority of junior doctors - but there are some elements at the very top of the BMA who are absolutely refusing to compromise."
Mr Hunt acknowledged that his position as Health Secretary was likely to be his last major role, as he defended his handling of the dispute.
"This is likely to be my last big job in politics. The one thing that would keep me awake is if I didn't do the right thing to help make the NHS one of the safest, highest quality healthcare systems in the world," he told the Today programme.
"Health secretaries are never popular. You are never going to win a contest for being the most liked person when you do this job. But what history judges is did you take the tough and difficult decisions that enabled the NHS to deliver high-quality care for patients. For me, that's what it's about."
David Cameron told ITV News the strike was "not right".
The Prime Minister said he supported Mr Hunt's handling of the strike and added: "There is a good contract on the table with a 13.5% increase in basic pay - 75% of doctors will be better off with this contract.
"It's the wrong thing to do to go ahead with this strike, and particularly to go ahead with the withdrawal of emergency care - that is not right."
Oliver Warren, a consultant colorectal surgeon at the Chelsea and Westminster Hospital NHS Foundation Trust, tweeted: "Update from frontline - all going well! 3 consultant ward round, all pts (patients) seen - morale high. Off to ED to review a pt #JuniorDoctorsStrike."
Kingston Hospital said: "We've got consultants from ITU (ntensive care), Medicine + Gynae caring for patients in A&E majors today #JuniorDoctorsStrike."
The Prime Minister's official spokeswoman said Mr Cameron was being "kept updated on the situation".
Asked whether the PM thought public support for the strikers was fading, the spokeswoman said: "If you look at the impact on patients today and the concerns about risk, I think people are asking 'is this an appropriate and proportionate response to take?'.
"On some of these issues at the heart of this, like the issue of Saturday pay, junior doctors earn more than ambulance workers, nurses, healthcare assistants, others in the public sector like police officers and firemen who also work on a Saturday.
"I think it's important that people understand that the contract that is being introduced on average will lead to an increase in basic pay of 13.5% and will not impose longer hours."
Asked whether ministers had the impression that the BMA was not prepared to negotiate further, the spokeswoman said: "There have been over 70 meetings over a number of years to try to resolve the issues and that hasn't been possible because, as the Health Secretary has said, they refuse to show any compromise on the issue of Saturday pay.
"The Health Secretary has written to the chair of the BMA asking to meet to discuss broader issues around working conditions for junior doctors because we would like to work with them on this and move forward.
"We've had three years of talks, there have been numerous concessions, we have done all we could to avoid these strikes. It has ultimately been a decision for the junior doctors to go ahead."
Betway said the odds of Mr Hunt resigning had fallen from 6/1 to 5/2.
The BMA's junior doctor chairman, Johann Malawana, described the walkout as "the saddest day in NHS history" on Twitter.
He said the action was "entirely avoidable", and that Mr Hunt had been unwilling to resume talks.
Early suggestions are that hospitals have been quieter than normal, with patients heeding warnings to stay away.
The TUC is being urged to organise a national day of action in support of the junior doctors.
The executive of the Public and Commercial Services union called for the idea to be discussed at a meeting of the TUC general council on Wednesday.
PCS general secretary Mark Serwotka said: "It is increasingly clear that the Government is deliberately stoking the dispute for political reasons, and that the BMA's brave response continues to be necessary in defence of patient safety.
"The junior doctors' determined action enjoys wide public support and deserves the fullest possible support and solidarity from the trade union movement."