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John Bolton was unable to win the necessary Senate support for him to continue in the job.
He took up the UN posting last year during a Congressional holiday after his nomination stalled in the Senate.
He is the second high-profile member of President George W Bush's team to leave after the Republicans fared badly in last month's mid-term polls.
Amid fierce opposition to Mr Bolton from Democrats and even some Republicans, Mr Bush had used a presidential power called a recess appointment to give him the job in August 2005.
It was a procedural maneuver that avoided the need for him to be confirmed until the end of this year.
That procedure cannot be repeated, and the new climate in Congress would make it all but impossible for him to win a two-thirds majority of senators.
Mr Bolton's critics said a man who once declared there was "no such thing" as the UN was hardly a suitable choice to join the body.
But his admirers said he was a bright, hard-working realist - whose skepticism about the UN's role made him an ideal envoy.
A White House spokeswoman said that among Mr Bolton's accomplishments, he assembled coalitions addressing
Photo Caption
John Bolton sits behind President Bush