Warnings that Britain leaving the EU would damage Western security have been backed by former Nato chiefs and senior Washington figures - in a boost to David Cameron.
Pro-Brexit campaigners led by Boris Johnson dismissed the Prime Minister's claim that peace in Europe could be threatened by a Leave vote - arguing Nato, not Brussels, had been the key to security.
In a concerted pitch to voters to back continued membership, five former secretaries general of the transatlantic alliance said pulling out would "give succour to the West's enemies".
And 13 former US secretaries of state and defence and national security advisers said Europe would be "dangerously weakened" and cautioned Britain not to believe its close ties with Washington would compensate.
In a speech setting out the "patriotic" case for a Remain vote, Mr Cameron said the 28-nation bloc had reconciled warring nations and was playing a crucial role in the fight against Islamic State (IS) and dealing with a "newly belligerent" Russia.
But former London mayor Mr Johnson said it was Nato which had been the protector of Europe's peace since the Second World War, and that the EU was "a force for instability and alienation".
In a letter to the Daily Telegraph, the former Nato chiefs said: "At a time of such global instability, and when Nato is trying to reinforce its role in Eastern Europe, it would be very troubling if the UK ended its membership of the European Union.
"While the decision is one for the British people, Brexit would undoubtedly lead to a loss of British influence, undermine Nato and give succour to the West's enemies just when we need to stand shoulder to shoulder across the Euro-Atlantic community against common threats, including on our doorstep."
The signatories were Lord Carrington, a decorated Second World War veteran who served as foreign and defence secretaries, ex-defence secretary Lord Robertson, Javier Solana, Jaap De Hoop Scheffer and Anders Fogh Rasmussen.
"Given the scale and range of challenges to peace and stability we collectively face, the Euro-Atlantic community needs an active and engaged United Kingdom," they said.
The concerns were echoed in a separate letter to The Times, signed by 13 former Washington officials representing every White House administration, Democrat and Republican, for the last 40 years.
"In our globalised environment it is critical to have size and weight in order to be heard," the group said.
Ronald Reagan's secretary of state George Shultz, ex-CIA chief and defence secretary Leon Panetta and Madeleine Albright, who served as secretary of state under Bill Clinton, were among those making the warning.
"The special relationship between our countries would not compensate for the loss of influence and clout that the UK would suffer if it was no longer part of the EU," they said.
"This would be true in foreign policy, defence policy and international trade matters, and other areas where the EU is indeed a significant voice."
Mr Cameron argued that while Nato remains the "cornerstone" of national defence, "top military opinion" was clear that the EU is a "vital" reinforcement to the organisation, he said.
Vote Leave said "claims that leaving the EU and taking back control would somehow lead to war smack of desperation" and insisted the safe option was to quit.
Mr Johnson - who gave his own speech in favour of Brexit little more than an hour after the PM's intervention - questioned the sincerity of Mr Cameron's warnings.
He was in turn criticised for appearing to blame the EU for Russia's annexation of Crimea - leading to accusations he was an "apologist" for Russian president Vladimir Putin.
Conservative former defence secretary Liam Fox said the warnings were out of date.
"A lot of those people are from a very different era to the one we are in now," he told BBC2's Newsnight.
"I can understand why they would have thought that then but I think we are entering into a very different period in terms of global security structures.
"The United Kingdom outside of the European Union would actually give an impetus to the political aspect of Nato, which I think has been long neglected, and give a bit of a kick to some of those countries who seem to believe that we can do the hard lifting in terms of hard power and they can do the soft power elements,"
He added: "My worry is that you have far too few European countries pulling their weight inside Nato, seeing the EU as some sort of soft option for them in terms of defence."