Italian Prime Minister Matteo Renzi resigned after suffering a heavy defeat in a referendum over his plan to reform the constitution.
In a late-night news conference, he said he took responsibility for the outcome, and said the No camp must now make clear proposals.
With most ballots counted, the No vote leads with 60% against 40% for Yes.
The turnout was nearly 70%, in a vote that was seen as a chance to register discontent with the prime minister.
"Good luck to us all," Renzi told reporters. He said he would tell a Cabinet meeting on Monday afternoon that he was resigning, then tender his resignation to the Italian president.
EU leaders won't have slept much on Sunday night. Angst about Italy makes an uncomfortable bedfellow and there's plenty for them to worry about. Particularly in Brussels. Prime Minister Renzi was the only premier left in Europe with a vision for the EU's future. Angela Merkel is too busy crisis-managing while much of France is in thrall to Front National Eurosceptic.
But Matteo Renzi is no more. The self-styled reformer with his promise to stabilize politics and kick-start the Italian economy has managed quite the reverse.
Italy wakes up on Monday to the threat of a banking crisis, political turmoil, and a group of anti-establishment populists banging on the doors of government.
Eurozone beware and EU be warned. Italy is the euro currency's third largest economy and it's in for a bumpy ride. And there are more unpredictable votes to come in 2017: in France, Germany the Netherlands and perhaps here in Italy too.
Matteo Renzi's staked his political future on his attempt to change Italy's cumbersome political system. He wanted to strengthen central government and weaken the Senate, the upper house of parliament.
His opponents - including some within his own party - had argued that the reforms would give the prime minister too much power. The electorate agreed.
But the referendum was more than a vote on constitutional reform, it was widely regarded as a chance to reject establishment politics.
It was a resounding victory for the No camp, a medley of populist parties headed by the Five Star Movement, which capitalized on Renzi's declining popularity, years of economic stagnation, and the problems caused by tens of thousands of migrants arriving in Italy from Africa.
Renzi will hand in his resignation to President Sergio Mattarella later on Monday, following a final meeting with his cabinet. So far, there has been little reaction from mainstream politicians.
Markets seemed to have taken Renzi's departure in their stride. Stocks and the euro fell in early trading in Asia but there were no signs of panic, as the possibility of his resignation had already been factored in.
Source: News Agencies, Edited by website team