Four Iraqis were killed and dozens wounded when U.S. tanks and helicopters descended on this holy city Friday and fired on positions held by fighters loyal to Muqtada al-Sadr (search), who blasted America in a sermon.

The U.S. attack represented the strongest push yet against the radical cleric, whose forces fought intense battles with American forces this week in another holy city, Karbala.

In response, al-Sadr's militiamen attacked U.S.-led coalition headquarters in Nasiriyah, trapping international staff and some Italian journalists inside. Explosions and gunfire rocked Karbala, and al-Sadr's top aides threatened to unleash more attacks across the Shiite south and in Baghdad.

Several large explosions and the roar of high-flying aircraft could be heard in Baghdad before dawn Saturday. The U.S. command issued no statement and the cause of the blasts was unknown.

Hamid al-Bayati, spokesman for a mainstream Shiite group represented on the U.S.-appointed Iraqi Governing Council, called the fighting in Najaf a "big mistake" that could inflame sectarian passions. He urged both sides to mediate an end to the standoff in this city, the most important center of Shiite theology and scholarship.

At least four Iraqis were killed and 26 wounded Friday in Najaf, according to Haidar Raheem Naama, a hospital official. He said most were civilian. One coalition soldier was wounded, U.S. officials said.

At least three militiamen also were killed, and their coffins were brought to the Shrine of Imam Ali for family and friends to pray for their souls.

"America is the enemy of God," fighters shouted.

Explosions and heavy machine-gun fire rocked Najaf for hours, and bands of gunmen carrying assault rifles, rocket-propelled grenades and mortar tubes roamed the city. After a lull, sporadic firing resumed as night fell.

Apparent gunfire slightly damaged one of Shia Islam's (search) holiest shrines, prompting calls for revenge and even homicide attacks.

Four holes, each approximately 12 inches long and 8 inches wide, could be seen on the golden dome of the Imam Ali mosque, burial place of Imam Ali Ibn Abu Talib, the Prophet Muhammad's cousin and son-in-law and the Shiites' most revered saint.

The mosque, in the middle of Najaf, is about 100 miles south of Baghdad on a high desert plateau overlooking the world's largest cemetery.

Militia members blamed the Americans for the damage to the mosque, but Brig. Gen. Mark Kimmitt (search), the chief U.S. military spokesman in Iraq, said al-Sadr's men were probably responsible: "I can just tell you by the looks of where we were firing and where Muqtada's militia was firing, I would put my money that Muqtada caused it."

During the crackdown on al-Sadr's al-Mahdi Army, U.S. forces have been careful to avoid damaging shrines for fear of enraging Iraq's Shiite majority. They have attacked mosques where insurgents have set up fighting positions.

At a press conference in Baghdad, Kimmitt pointed to a map of Najaf and said a U.S. convoy might have been fired on from the cemetery as it moved near the shrine. If so, those rounds could have hit the shrine, he said.

Kimmitt accused the militia of using religious sites "much like human shields." He said American forces had not initiated the fighting but were responding to attacks by al-Sadr's gunmen.

That did little to assuage the anger of many Shiites in Najaf. By early evening, thousands gathered around the Imam Ali shrine to inspect the damage. Some shook their heads in disbelief. Others mumbled prayers.

"The Americans had better leave Iraq after this," said Jassim Mohammed. Another man, Abu Zahraa al-Daraji, added: "The Americans have crossed a red line."

Al-Sadr's aides called on their followers to rise up against the coalition. His representative in Nasiriyah, Sheik Aws al-Khafaji, threatened attacks on coalition forces there, most of whom are Italians.

After his threat, armed men attacked coalition headquarters in Nasiriyah, about 200 miles southeast of Baghdad. They fired at least five rocket-propelled grenades within a half hour as Italian troops and Filipino security guards fought back.

About 10 coalition staffers, including Italians, Americans and Britons along with 10 drivers and security guards were trapped in the building along with four Italian journalists, coalition officials said.

Explosions and gunfire also rocked another Shiite holy city, Karbala, as U.S. soldiers clashed with al-Sadr's militiamen. Shops were closed and residents stayed off the streets.

In Baghdad, aides to al-Sadr urged followers in Sadr City to travel to Najaf to reinforce the militia. Al-Sadr's representative in the southern city of Basra, Sheik Abdul-Sattar al-Bahadli, said he would form suicide squads to carry out attacks on coalition forces and urged residents to register for the squads starting Saturday.

And in the southern city of Amarah, al-Sadr aide Farqad al-Mousawi warned Iraqi police and civil defense corps members that they risked assassination if they helped U.S. soldiers fight al-Sadr's militia.

Japan's Kyodo News service reported shooting erupted late Friday in the center of Samawah, a southern city where Japanese and Dutch troops are based. The shooting broke out after armed al-Sadr supporters began sealing off streets in the downtown area.

Al-Sadr launched an uprising against the coalition last month after U.S. officials announced he was wanted for the April 2003 murder of a cleric in Najaf. He lacks the spiritual stature of Grand Ayatollah Ali al-Husseini al-Sistani, and his confrontational tactics have exasperated moderate Shiites.

However, al-Sadr commands the support of thousands of mainly poor, urban Shiites who admire his father, a grand ayatollah who was killed by Saddam Hussein's agents. Al-Sadr has also capitalized on hostility toward the coalition following revelations of abuse of Iraqi prisoners by U.S. soldiers.

Despite the fighting, al-Sadr delivered a sermon at Friday prayers in Kufa, another holy city that lies six miles to the northeast of Najaf, as he has for the past four Fridays.

Al-Sadr described President Bush and British Prime Minister Tony Blair as "the heads of tyranny" and accused them of ignoring the suffering of Iraqis in coalition prisons while drawing attention to what he described as the "fabricated" case of Nicholas Berg, an American civilian who was beheaded by militants.

The Associated Press contributed to this report.