The British government's director of communications and stragegy, Mr Alastair Campbell, is to resign.
No date has been set for his departure and his successor has not been named, a statement from Downing Street statement said.
Mr Campbell, a close ally of Prime Minister Tony Blair for almost a decade, helped orchestrate two landslide election victories. He said he wanted to hand over to a successor "in the next few weeks".
Often described as the "real deputy prime minister", Mr Campbell played a key role in drafting a government dossier on Iraq's weaponry which has been subject to scrutiny in the inquiry into last month's suicide of weapons expert Dr David Kelly. The investigation has sent Mr Blair's public trust ratings plunging.
Mr Campbell said in a statement: "We agreed on April 7th this year that I would definitely leave this summer and I have now given the prime minister formalnotice of my decision to leave."
Mr Campbell said his family had paid a price for his role and said his partner, Ms Fiona Millar, would be leaving No 10 at the same time "in a few weeks".
Mr Campbell said he did not want to take on "another big job" but hoped to write, broadcast and make speeches.
He said: "It has been an enormous privilege to work so closely in opposition and in government for someone I believe history will judge as a great transforming prime minister."
Mr Blair, describing Mr Campbell as "an immensely able, fearless, loyal servant of the cause he believes in" said his contribution to Labour's electoral success was enormous.
"In the extraordinarily difficult and wearing world of the modern media, he operated with tremendous skill and dedication," Mr Blair said. Agencies