Ayatollah Sistani is said to have an uneasy relationship with Mr Sadr
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Iraq's most senior Shia cleric says all armed forces must be withdrawn from the holy cities of Najaf and Karbala.
Grand Ayatollah Ali al-Sistani made the request in his first statement since radical Shia cleric Moqtada Sadr began an insurgency against US-led forces.
It follows pitched battles last week close to Shia Islam's holiest sites.
Correspondents say Mr Sistani's involvement is directed more at Mr Sadr who has asked militant supporters to converge in the two cities.
Dozens of people have been killed in clashes between the US-led coalition and Mr Sadr's Mehdi Army since the insurgency began a month ago.
The radical cleric is wanted in connection with the assassination of a rival Shia cleric.
Dangerous times
On Sunday, clashes took place close to the revered Imam Hussein and Imam Abbas shrines in Karbala.
Up to 15 US tanks took up position near the shrines while helicopters flew overhead.
Ayatollah Sistani said this was too dangerous.
Moqtada Sadr's militia have used shrines to mount operations
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"It's permissible... to demand the withdrawal of all military vestiges from the two cities and allow the police and tribal forces to perform their role in preserving security and order," Mr Sistani said in a rare statement released by his office in Najaf.
"The office of Ayatollah Sistani calls on citizens in all of the cities and governorates not to head to holy Najaf due to the dangerous circumstances that the holy city is passing through," the statement said.
It urged protesters to convene in mosques and provinces around the country, "to protest violations of the sanctity of the two holy cities".