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The threat by Cameron's ministers to back a UK exit in a referendum on the EU raised doubts in Washington on whether Britain would still be part of the deal once it had been negotiated. More immediately, Obama administration officials were concerned that the uncertainty over Britain's future would further complicate what is already a hard sell in Congress, threatening a central pledge in the president's State of the Union address in February.
With formal negotiations expected to start within weeks, the state department already has hundreds of staff working on the partnership. Sources at US-UK meetings in London last week said American officials made it clear that it would take a monumental effort to get TTIP through a suspicious Congress and that "there would very little appetite" in Washington to do it all again with the UK if Britain walked out of Europe.
US officials say that the White House is particularly perplexed because Britain played a key role in persuading Obama to stake significant political capital on the ambitious transatlantic partnership. If it is successful it could be the biggest trade and investment deal in history, encompassing half the world's GDP and a third of its trade.