Nick Clegg has attacked the prime minister, saying Gordon Brown is "not in control".
The leader of the Liberal Democrats told the BBC that there is a "fundamental question" about whether this administration is able to govern.
His criticisms of the Labour government came as communities secretary Hazel Blears announced that she was resigning from her cabinet post.
Ahead of the expected government reshuffle, Clegg said the departure of government ministers was "unsettling" for the public.
"I think this is now moving beyond personalities, beyond policy differences," he said.
Clegg argued that there is now a more fundamental question about whether "this government can govern".
"You have a prime minister in power who is in Number 10 but he is not in control," he said. "This is very unsettling for people."
He added: "I think we now need to bring this to a head. I think that when it gets to the position where very basic questions are being asked about whether Britain is being governed at all.
"When you see the spectacle of a cabinet, a governing party, half of which seem to be heading for the exit door and half of which seem to be plotting for what happens next."
Clegg also denied suggestions that his party lacks a structure for disciplining its MPs over their expenses claims.
"The wrong thing to do was to set up a committee of party apparatchiks sitting behind closed doors," Clegg said. "Calling them a star chamber, and as grand as you like, that is basically what it is."
Lib Dem MPs were being referred to the independent standards commissioner for judgement instead, he said.
"I don't think that politicians should act as judge and jury for their own misdemeanours," he told BBC Radio 4's Today programme.
And he warned that there would be an "understandable" backlash against all parties at the forthcoming elections.
"We are the only party in British politics saying unambiguously that we are stronger together in Europe and poorer apart," he said.

Dods Parliamentary Communications Ltd