KARBALA, Iraq — U.S. tanks, helicopters and jets attacked fighters loyal to a radical Shiite cleric in this holy city Wednesday, partially destroying a mosque used by insurgents and setting seven hotels ablaze. Twenty-two militants were killed.

The cleric, Muqtada al-Sadr, urged his followers to resist and compared their struggle to the Vietnam War in his first news conference since the standoff began more than a month ago.

American forces killed 22 militants, and six coalition soldiers were wounded, U.S. Brig. Gen. Mark Kimmitt said in Baghdad. Four of the soldiers returned to duty.

Iraqi leaders in another holy city, Najaf, discussed how to peacefully resolve the confrontation between al-Sadr and the U.S.-led coalition, which is seeking to arrest al-Sadr in the murder of a rival cleric. Coalition officials have said they welcome efforts to work for a peaceful solution, even though they will not negotiate with the cleric and want him to face justice.

Half of the Mukhaiyam mosque in Karbala was destroyed in the fighting. Most shops in Tal al-Zeinabiya, a central market, and three ambulances and two military vehicles also were destroyed.

Fighting subsided by dusk as the call for evening prayers spread across Karbala from loudspeakers at the Imam Hussein mosque, one of the most sacred shrines of Shia Islam.

Iraqi guards manned the shrine gates to prevent al-Sadr's fighters from entering. Explosions and machine-gun fire continued intermittently as night fell. Fighters pushed a wounded comrade down a street on a pushcart. Jets flew overhead as militiamen took up new positions near another holy site, the Imam Abbas shrine.

Al-Sadr's fighters acknowledged they lost control of the Mukhaiyam mosque, less than a mile from the Imam Hussein shrine.

"We put up a very stiff resistance," said Ameer Latif, a 30-year-old militiaman. Another fighter, Amar Haider, leaned against a wall with his Kalashnikov rifle and said: "God willing, we shall still be victorious."

Late Wednesday, three explosions resounded in Najaf, and residents said U.S. forces appeared to be making an armed incursion into the city. At least one civilian was killed and another was wounded, Iraqi authorities said.

Al-Sadr is holed up in Najaf. He met with reporters there Wednesday — his first press conference since his militia, the Al-Mahdi Army, launched attacks on coalition troops in Baghdad and other cities in early April.

"I appeal to the fighters and mujahedeen in Karbala to stand together so as none of our holy sites and cities are defiled. We are prepared for any American escalation and we expect one," al-Sadr said.