Moqtada Sadr lost a key aide on Friday, shot dead in Najaf
Radical Iraqi Shia cleric Moqtada Sadr has said the US will always be his enemy "till the last drop of blood".
Mr Sadr was responding to a statement by US Defence Secretary Robert Gates, who said that all those within the political process were not enemies.
"I have no enemy but you. You are the occupier," Mr Sadr's statement said.
Iraqi forces have been clashing with militias such as Mr Sadr's Medhi Army since last month. The US said 13 gunmen were killed in Baghdad on Saturday.
The latest fighting was in Baghdad's eastern Sadr City suburb, a stronghold of supporters of Moqtada Sadr.
On Friday, Riyad al-Nuri, a relative and key aide of the cleric, was killed by gunmen in the city of Najaf
The cleric blamed the US "occupation" for Mr Nuri's death.
In his statement on Saturday, Moqtada Sadr said: "I heard the statement of the terrorist American defence minister and I feel compelled to give a decent response to such a terrorist. I have no enemy but you. You are the occupier."
At the Pentagon on Friday, Mr Gates referred to Mr Sadr as a "a significant political figure".
Mr Sadr called a ceasefire with US-led forces in August last year, which Washington has cited as a key contributing factor to lower levels of violence.
"Those who are prepared to work within the political process in Iraq, and peacefully, are not enemies of the United States," Mr Gates said.
Iraqi forces launched an offensive in Sadr City a week ago
"[Mr Sadr] has a large following. And I think it's important that he become a part of the process if he isn't already."
But Mr Sadr asked: "Which political process do you want to involve me in when you are occupying my land?"
He said he would continue resisting the US presence in a "way that we consider suitable".
He urged the Iraqi government to "rid the land of the occupier" but said his followers should not "raise your weapons against Iraqis as long as they don't help the occupier".
Saturday's fighting in Sadr City was some of the worst there since Iraqi forces launched an offensive a week ago, residents said. US forces used both tanks and air support.
In Najaf, a curfew remained in place after the murder Mr Nuri.
Hundreds of people have died in clashes between Iraqi forces and militias, mainly in Baghdad and in Basra in the south, since Prime Minister Nouri Maliki ordered his crackdown on armed gangs.