Fierce fighting between U.S. and Iraqi forces and Shiite rebels loyal to cleric Moqtada Sadr escalated in five cities Friday, in a second day of combat resembling the Sadr-led uprising of last spring.

U.S. and Iraqi forces, along with British and Italian troops, have killed about 300 Iraq militants in two days of fighting in Najaf, the U.S. military said Friday. The military also announced that two Marines were killed Thursday during combat with the rebels in Najaf. Thursday the military had reported one death.

Meanwhile, wire services reported that Grand Ayatollah Ali Sistani, Iraq's most influential Shiite Muslim cleric and a relative voice of moderation, arrived in London Friday for treatment of a heart condition.

"The ayatollah suffered a health crisis related to his heart a few days ago," his spokesman in Beirut Sheik Hamed Khafaf told the Associated Press.

Sistani's absence could leave a critical vacuum of leadership in the country's majority Shiite community.

And in Iraq's Sunni Muslim triangle west of Baghdad, the governor of Anbar Province, which includes the volatile cities of Fallujah and Ramadi, appeared on television in the company of men in masks and announced his resignation, a week after insurgents set fire to his house and kidnapped three of his sons.

Abdul Karim Rawi, shown on the al-Jazeera cable television network, read a statement saying he "repented" his cooperation with the "infidels." He looked grim, ashen-faced and under duress, although it was unclear whether he was in captivity.

A second day of clashes were reported Friday in Najaf, Basra, Nasiriyah, Amarah and in the Sadr City district of Baghdad itself, which is the Shiite cleric's stronghold.

The worst appeared to be in Najaf, where TV footage showed U.S. helicopters firing at targets within the city and plumes of dark smoke rising in the sky as masked militiamen from Sadr's Mahdi Army ran through the streets firing weapons.

Hospital officials in Najaf reported at least 10 dead Iraqis and another 40 wounded.

Shiite rebels have long warned that they would respond violently to any attack on Najaf -- home to several important shrines important to Shiites worldwide.

After hearing about the situation in Najaf, people poured into the streets in Sadr City, where there was fighting between militiamen and Iraqi forces.

U.S. troops ringed Sadr City with tanks but did not enter the area, which appeared to still be under the control of Mahdi Army militiamen stationed at numerous checkpoints in the densely populated neighborhood.

"Najaf is now under siege," said Ahmed Shaybani, a spokesman for Moqtada Sadr. "We call on the Islamic world and on the entire world to intervene and solve this problem. The revolution will continue as long as the occupation forces keep bombing the city."

One militiaman, Khadim Mohammed, 39, said his forces had received orders to be prepared to fight after hearing the news from Najaf. He said U.S. planes and helicopters had fired into Sadr City during the night, but that could not be confirmed independently.

Rebel cleric Sadr had called on his supporters Thursday to rise up anew against U.S.-led security forces, after a fragile two-month truce in Najaf ended with clashes that brought down a U.S. helicopter.

Sadr's militia said Thursday it had gained control of Najaf, Amarah, Nasiriyah and Basra although Iraqi officials denied that the fighters had taken the cities.

Sadr's call for an uprising was his first significant test of Iraq's new interim government, which took office June 28, and signaled the end to the uneasy peace that had settled over Iraq's long-oppressed Shiite Muslim majority in the southern part of the country.

It wasn't clear whether the call would result in a broad revolt. In April, Sadr rallied his supporters to strike against the U.S. occupation, leading to two months of clashes that left hundreds dead. Many here said they would listen closely to the messages Shiite clerics deliver during Friday prayer services for an indication of what might happen this time.

Some of those services were fiery Friday. In his sermon, Sheikh Nasser Sadi denounced the Iraqi interior minister, accusing him of escalating the situation in Najaf.

"We call on all Iraqi people to protest the violations of our holy shrines," he said. "We appeal to Shiites and to the Islamic world to rise up and defend their shrines."

Interior Minister Falah Naqib pledged Thursday in Baghdad to find and arrest Sadr.

"We will not negotiate," he said at a news conference. "We will fight these militias. We have power to stop these people, and we'll kick them out of the country."

The U.S. military and Iraqi police said the fighting in Najaf Thursday began when Mahdi Army fighters attacked a police station overnight. The military said Iraqi forces called for help to resist the attack.

"If they want it to be war, let it be," said Ghalib Hashim Jazaeri, the police chief in Najaf. "We have enough men and equipment to defeat them."

Each side blamed the other for breaking a truce negotiated in June to end the two-month uprising.

"They broke the truce," Jazaeri said. "They want to occupy the city. We cannot let them do that. If they attack us, we will defend ourselves."

Mahdi Army fighters in the streets of Najaf shot off grenades and set up roadblocks with mortar tubes and tires. A voice over a loudspeaker coming from the shrine of Ali, one of the holiest sites in Shiite Islam, urged residents to take up arms to defend the city.

Shaybani denied that Sadr's followers had started the fight. He said the Iraqi police and National Guard and U.S. forces had broken the truce, which restricted U.S.-led forces from entering parts of the city, including areas near sacred sites.

Shaybani said the occupation forces surrounded the city about 2 p.m. Thursday. "We knew they wanted to invade it," he said. "We had and have to defend the holy city. We didn't want to violate the truce, and we are still committed to it. But they don't respect the word they gave. They want it to be war."

As a large plume of smoke rose from the city, a black U.S. helicopter tilted to one side and chugged slowly to the ground at an angle before it hit with a loud boom. Sadr's aides said the Mahdi Army shot down the aircraft, the Reuters news agency reported. The U.S. military said two crew members were wounded and had been evacuated.

Naqib said the decision for Iraqi forces to fight Sadr's militia came from the governor of Najaf province, not the U.S. military. On that point, Sadr's spokesman agreed.

"We were forced to do this after the governor started his stupid idea to invade the city," Shaybani said Thursday.

Fred Barbash reported from Washington.