Ann Taylor, Shadow Leader of the House, said there was "a complete sense of disintegration" about the Government.
"If the Prime Minister clearly believes that he doesn't have the confidence of his own party then he clearly does not have the confidence of this House.
"We want to know with what authority ministers can speak from the despatch box? We need to know when ministers are speaking as ministers and when they are speaking as candidates in the election."
Party whips and Cabinet ministers, including Stephen Dorrell, John Redwood and Jonathan Aitken, joined the rush into the chamber following Mr Major's statement to the Downing Street press conference.
Deputy speaker Dame Janet Fookes fielded a succession of points of order, repeatedly emphasising the constitutional distinction between party leader and Prime Minister.
Mr Dorrell, in the only contribution from the Government front bench, said Mr Major had observed that essential distinction. The announcement "does not affect his status as the Queen's first minister".
Menzies Campbell, for the Liberal Democrats, said Mr Major's resignation was unprecedented in modern political times and raised fundamental questions. "I don't think such an event has happened in this century."
Dennis Skinner, MP for Bolsover, said: "If Mr Major has lost the confidence of the governing party in this House, he has a duty to go to the Queen and call a general election so the country can decide."
There were few Tory contributions, but Robert Spink, MP for Castle Point, said Mr Major had made a brave move. "It is a very clever move and it's a move he will win."
Mr Major gave no hint of his decision when, less than two hours earlier, he was tackled by Tony Blair about "bitter in-fighting" in the Tory party.
The Labour leader asked if the Prime Minister agreed with Sir Patrick Mayhew, Secretary of State for Northern Ireland, who complained in a letter to the Times about some Conservatives destabilising the Government.
Mr Major said Sir Patrick was "an honourable friend in every sense of the word" and he was "immensely grateful for his continued support".
But Mr Blair pressed: "It surely comes to something, doesn't it, when you get a Cabinet minister driven to writing to the Times about divisions in his own government without telling the Prime Minister.
"If even Cabinet ministers decide the bitter in-fighting is damaging the national interest, why won't the people of Britain conclude the Conservative Party is no longer fit to govern the country?" he asked
Mr Major responded by attacking Labour divisions on education, pointing to criticism by Roy Hattersley, the former deputy Labour leader, of the U-turn on grant-maintained schools. Mr Hattersley had "a little bit of bitter in-fighting of his own" about party policy.Reuse content