At least 75 people are now feared dead and more than 100 injured following a car bombing during prayers at the Imam Ali mosque in Najaf, the most holy shrine for Shiite Muslims in Iraq.
Najaf has been the site of considerable unrest among the religious communities in the holy city, 110 miles south-west of Baghdad.
One of Iraqi's most important Shiite clerics, Mohammed Saeed al-Hakim, has been killed in the attack, which, it is understood, had targetted him.
He had been the target of another attack last month, when a bomb exploded outside his house, killing three guards and injuring 10 others including family members.
Iraqis dug among rubble strewn with body parts for survivors and angry Shi'ites vowed to avenge the attack which killed Ayatollah Mohammed Baqer al-Hakim and other worshippers as they were leaving the Imam Ali mosque in Najaf after Friday prayers.
Eyewitnesses said Hakim, head of the Supreme Council for the Islamic Revolution in Iraq (SCIRI) and the leading Shi'ite figure in Iraq, was about to drive away when the blast went off, destroying his car.
The attack was the latest in a series of bloody incidents in Najaf, several of them aimed at religious leaders of the Shi'ite branch of Islam followed by the majority of Iraqis.
Hakim's co-operation with the US-led administration through its Governing Council was seen as crucial to a successful transition to democracy in Iraq.
"The world is going to be turned upside down after this. This is our holiest site," said Qusay Jaber outside the mosque in the central Iraqi city. "If the Americans don't secure our sites anything is possible. We will stage an uprising."
The Imam Ali mosque holds the tomb of Ali, a son-in-law and cousin of the Prophet Mohammed, and is the most sacred Shi'ite site in Islam. It suffered some damage in the blast.