Top White House spokesman Robert Gibbs is to step down by the end of February.
He is to work as an outside consultant on Barack Obama's 2012 bid for re-election as president and be a voice for him outside the White House.
Mr Gibbs has been at Mr Obama's side since the former Illinois state politician ran for the US Senate in 2004.
So far, no replacement has been named. Likely candidates include his deputy Bill Burton and Vice-President Joe Biden's spokesman Jay Carney.
He is the latest in a series of aides to leave the administration.
Others include White House chief of staff Rahm Emanuel, who is campaigning for the mayoralty of Chicago, and the head of the National Economic Council Larry Summers.
Political strategist David Axelrod will also leave soon to join Mr Obama's re-election campaign.