The four men are reported to have admitted to the bombing.
The local governor said two of the men were supporters of Saddam Hussein.
Crowds have gathered at the scene of the blast - the Imam Ali Mosque in Najaf - to prepare for the funerals of many of the victims.
A BBC reporter said the crowds were blaming Saddam's supporters for the blast but also blame Americans for not protecting them properly.
United Nations Secretary General Kofi Annan has called for Iraq's many political and religious groups to be calm.
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