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In a televised address to the nation, he demanded that the French people back his programme of reform - or accept his resignation. He said the choice would be made in a referendum later this year.
In the speech, he said the nation was "on the brink of paralysis", and warned of civil war if the situation continued.
Violence within minutes
Eight million workers - a third of the country's workforce - are now on strike, at the start of a third week of social unrest.
Within minutes of President de Gaulle's speech, riots erupted again in Paris, Lyon, Nantes, Bordeaux and Strasbourg.
In Lyon, a policeman became the first person to die in the demonstrations. He was run over by rioters driving a lorry into a line of riot police.
Crowds of spectators
The largest demonstration was in Paris, where an estimated 50,000 workers followed the traditional workers' route from the Place de la Bastille to the Place de la Republique.
They were cheered by crowds of spectators who lined the pavements.
But violence erupted when students broke through police cordons guarding bridges across the Seine.
Armed with Molotov cocktails, they advanced on the French stock exchange, the Bourse, shouting "The Bourse belongs to the workers!" and "Occupy the Bourse!"
They broke down the doors of the building and smashed windows, stuffing burning rags inside.
As students on the street outside sang the Communist revolutionary song, the Internationale, the Red Flag was hoisted above the building.
Police used tear gas to cut a passage for fire engines, but rioters made barricades of overturned cars and linked hands around the vehicles to stop firefighters running out their hoses.
By 2230 (2030 GMT), however, the fire was out, leaving the main floor of the stock exchange badly damaged.
Running battles between the police and demonstrators are continuing, with casualties already in the hundreds.
The Latin Quarter of Paris is effectively a siege camp, and there is no sign of an end to the demonstrations which are already being called France's second revolution.
President de Gaulle was persuaded not to hold a referendum by his Prime Minister, and eventual successor as President, Georges Pompidou.
Summit negotiations between the government, employers and unions began the day after the President's address, and negotiated a deal to raise wages.
But this was rejected by the striking workers, and the demonstrations got steadily worse until Mr Pompidou sent tanks into the outskirts of Paris on 29 May, for fear of a revolution.
General de Gaulle then called an election for the end of June. The demonstrations died away as campaigning got under way, and de Gaulle's party won a huge majority as public opinion appeared to turn against the strikers.
The new government announced major reforms to the education system - 67 new universities, and a more democratic system of governing councils.
General de Gaulle finally resigned in the following year, 1969, after staking his reputation on a referendum on political reform, which he lost.
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