Pressure is growing on Gordon Brown over his handling of the economic crisis after the US treasury secretary rejected the PM's plans for a 'bank tax'.
Timothy Geithner told Sky News he was "not prepared" to support a global tax on financial transactions.
At the G20 summit in St Andrews on Saturday, the Prime Minister urged leaders to consider the levy to protect taxpayers and make banks more accountable.
The money collected could be held in a global fund to bail out failed banks, Mr Brown suggested.
But speaking exclusively to Sky's Jeff Randall, Mr Geithner said: "That is not something that we're prepared to support."
He added: "I think we all share a basic interest in trying to make sure we build a system where taxpayers aren't exposed in the future and where the financiers are bearing the consequences of their mistakes - that they are responsible for the risks they take."
The humiliating rebuff was the first of several from leading figures in world finance.
The head of the International Monetary Fund (IMF) Dominique Strauss-Kahn said introducing such a tax "is very difficult for a range of reasons, in fact it is impossible".
But the Government insists Mr Brown has succeeded in opening a vital dialogue on how to deal with the global downturn.
Officials said simply because an idea does not get immediate approval does not mean it will not happen in the end.
While the transaction tax has its detractors, it also has its backers.
The French finance minister, Christine Lagarde, said it would be "a very good thing".
Chancellor Alistair Darling also went in to bat for the PM.
"I think there is broad agreement amongst countries that the institutions that have contributed so much cost to taxpayers should also be prepared to meet that cost when times are good," he said.
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