The head of the team searching for weapons of mass destruction in Iraq, David Kay, has resigned.
Mr Kay cast doubt on Iraq's weapons programmes
Mr Kay said he did not believe Iraq possessed large stockpiles of chemical or biological weapons.
He is being replaced by a former deputy head of the United Nations weapons inspections team, Charles Duelfer.
Mr Duelfer said earlier this month he believed the chances of finding chemical or biological weapons in Iraq were now "close to nil".
Mr Kay gave no reason for leaving, but the BBC's Jon Leyne in Washington says sources there speak of a mixture of personal reasons and his disillusionment with the weapons search.
His resignation had been expected for a few weeks.
The Iraq Survey Group (ISG) team leader was appointed by the Central Intelligence Agency (CIA) last June to head the post-war search for chemical, nuclear and biological weapons in Iraq.
The issue of banned weapons was the central element of the US case for invading the country.
No WMDs have been found in Iraq
In an interview with Reuters news agency after his resignation was announced, Mr Kay said he did not believe there had been large-scale production of chemical or biological weapons in Iraq since the end of the first Gulf War in 1991.
"I don't think they existed," Mr Kay said.
"What everyone was talking about is stockpiles produced after the end of the last Gulf War and I don't think there was a large-scale production programme in the 90s."
"I think we have found probably 85% of what we're going to find."
Our correspondent says these are powerful remarks from someone who once strongly believed Iraq's weapons of mass destruction (WMD) represented a major threat.
In his recent State of the Union address, US President George W Bush quoted the conclusion of Mr Kay's interim report, which said only that WMD-related programme activities had been found in Iraq.
The Bush administration has not officially reacted to Mr Kay's latest remarks but correspondents say this is a serious embarrassment for the White House. On Thursday, Vice President Dick Cheney said he still had not given up hope of finding WMDs in Iraq.
Leading Democrats have seized on Mr Kay's remarks.
Mr Duelfer is widely respected in the arms control field
"It increasingly appears that our intelligence was wrong about Iraq's weapons, and the administration compounded that mistake by exaggerating the nuclear threat and Iraq's ties to al-Qaeda," said Senator John Rockefeller, the senior Democrat on the Senate Intelligence Committee.
"As a result, the United States is paying a very heavy price."
Jane Harman, of the House of Representatives intelligence committee, said Mr Kay's comments pointed to a massive intelligence failure and could not be ignored.
On Friday, the new ISG group head, Mr Duelfer, distanced himself from his comments on US television earlier this month in which he expressed doubts that banned weapons would ever be found.
"I have now been given the responsibility of being in charge of the investigation and I don't know what the outcome will be. I don't want to pre-judge that," he said.
Mr Duelfer, 51, served as deputy executive chairman of the UN Special Commission on Iraq from 1993 to 2000.