The resignation of all the Shi'ite ministers from the 24-member Western-backed cabinet came two days before it was scheduled to discuss a draft UN document setting up a tribunal to try the killers of former Prime Minister Rafik al-Hariri.
Many Lebanese blame Syria for Hariri's killing but Damascus denies involvement.
While the resignations will not bring down the government, they pose a major challenge to the majority anti-Syrian coalition in a country where the political system is based on a delicate sectarian balance.
''To pave the way for the majority to practice what it wants freely and so that we don't cover what we are not convinced of ... we announce the resignation of our representatives in the current cabinet,'' Hezbollah and Amal said in a joint statement.
The two groups allied to Syria said the anti-Syrian majority had rejected their demands for a decisive say in government during week-long talks that collapsed earlier in the day.
The escalating political crisis could provoke confrontation on the streets of Beirut at a time of rising tension between Sunni and Shi'ite Muslims.
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