The Remain campaign's use of "spin, smears and threats" risks damage to its members' integrity that will haunt them beyond the referendum, Iain Duncan Smith has warned.
The Work and Pensions Secretary said he found the acrimony emerging between the factions "troubling" and accused rivals of using "desperate and unsubstantiated claims".
He criticised the pro-EU camp's case for being largely supported by a "nightmare" image of Britain's chances outside the EU, with "biblical consequences" resulting from a vote to leave.
Mr Duncan Smith accused the Government and Remain campaign as staging a "series of stunts" using big business, finance chiefs and European leaders to "bully" those considering a vote to leave into fearing for their future prosperity and security.
However the former Tory leader appeared to row back from an earlier assertion that a Government analysis of how Britain would operate outside the EU was a "dodgy dossier".
He wrote: "The Remain campaign's case seems almost wholly based on what they describe as the nightmare of leaving.
"This case has in whole or in part become characterised by spin, smears and threats ... In the last fortnight we have had a series of highly questionable dossiers – threatening almost biblical consequences if we dare to consider a future outside of the European Union.
"We've seen a series of stunts, whereby big businesses, big banks, and powerful politicians from other EU member states seek to bully the British people into believing their jobs and security are at risk."
He made the comments in the Daily Mail after French president Francois Hollande warned of the "consequences in many areas" should Britain choose to leave the EU.
On Wednesday it emerged BMW's chief executive, Torsten Muller-Otvos, had written to Rolls-Royce employees indicating that its "employment base" could be affected if Britain could not secure a good deal outside the EU.
Mr Duncan Smith said the debate ahead of the June 23 referendum had to be conducted with respect and warned rivals not to "indulge in scaremongering".
He warned against painting Eurosceptic thinking as "heretical and dangerous" as he expressed fears over the after-effects of an embittered referendum campaign.
He wrote: "The acrimonious manner in which all this has been conducted is troubling, and will I fear have consequences long beyond June 23.
"After all, such desperate and unsubstantiated claims are now being made that they begin to damage the very integrity of those who make them in the eyes of the public."
According to reports Britain Stronger in Europe are to launch an initiative to increase their share of the "grey vote" - by encouraging young people to persuade their grandparents to vote "in".
Education minister Sam Gyimah told The Times: "The way for this campaign to really come alive is to have grandparents talking to their children and grandchildren about the future of this country."
Polls used by the newspaper showed almost seven in 10 pensioners wanted to leave the EU and young people are more likely to be pro-European - although they are less likely to cast a vote,
"The referendum matters for this generation in particular because they have got more of their life ahead of them," Mr Gyimah said.