German central bank boss Axel Weber will step down from the role at the end of April, the German government says.
The decision to leave the Bundesbank follows a meeting with German chancellor Angela Merkel.
There had been rumours that Mr Weber was not going to put himself forward to replace Jean-Claude Trichet as head of the European Central Bank (ECB).
Mr Weber had been seen as a front runner to succeed Mr Trichet, who steps down this year.
Berlin said the move was being made "for personal reasons" and that a successor would be named next week.
But there was no mention of the ECB position in the German government statement.
He has been vocal in his opposition to the ECB's policy of stepping in to buy government bonds from countries with high debt levels.
It has done this if international investors have either shied away from buying government debt, or demanded too high a rate for it.
The bank bought Portuguese government bonds on Thursday after yields rose to record highs in early trading, sparking renewed fears about Portugal's ability to raise money on the international markets.
Yields fell quickly after the ECB's intervention.
Opposition to this policy puts Mr Weber at odds with many European central bankers. However, he does hold the advantage of running the central bank of Germany, Europe's strongest economy.