Colin Powell's decision to step down as US Secretary of State will prompt worries that President George Bush's new-look administration will adopt an increasingly hardline approach to foreign affairs.
The early indications emanating from the White House are that national security adviser Condoleezza Rice is the most likely candidate to succeed Mr Powell.
Other names in the frame include America's UN Ambassador John Danforth, a religious conservative. Paul Wolfowitz, the deputy defence secretary, and regarded as a hardliner, is also being mentioned.
Commentators in Washington believe that any of the candidates would more accurately reflect the mindset at the very top of the Bush administration than the Mr Powell.
The former soldier had a controversial tenure in the secretary of state's job, reportedly engaging in repeated run-ins over policy with the influential Defence Secretary Donald Rumsfeld and Vice President Dick Cheney.
Reaction to his departure today was wary.
New Mexico governor Bill Richardson, a former UN ambassador in the Clinton administration, cautioned: "Secretary Powell's departure is a loss to the moderate internationalist voices in the Bush administration.
"Hopefully, his replacement will be a pragmatist rather than an ideologue." Arab League Secretary-General Amr Moussa told CNN that Mr Powell was a "voice of moderation" in the Bush administration.
His spokesman, Hossam Zaki, added: "We hope the coming secretary would be someone who can equally understand the region."
Palestinian Cabinet Minister Saeb Erekat said Powell will leave his "mark."
"In our deliberations with Secretary Powell he gained our highest respect and appreciation through his fairness and through dealing in a very highly dignified manner," Mr Erekat said.
"He will leave his mark on international politics and we really do hope that in President Bush's second term every effort will be exacted in order to realize President Bush's vision of a two-state solution on the ground."
In London, Foreign Secretary Jack Straw stressed Mr Powell's internationalist outlook as he delivered his tribute to his work.
Mr Straw described Mr Powell as "a man who has been tireless in his work for the US, tireless in his work for Nato and the transatlantic alliance, tireless in his work for peace in the world ...
"He has had a great many successes to his credit: the fact that there was an international consensus developed so swiftly in respect of Afghanistan; the fact that the US agreed to put the whole issue of Iraq back before the United Nations and that we were able to achieve resolution 1441 at the beginning of November 2002 was above all due to his indefatigable efforts in negotiating that resolution line by line.
"And then, perhaps above all, although the situation in the Middle East has been very frustrating, it was he who encouraged the US government to go down the path of the two-state solution. President Bush became the first US President ever to recognise that there has to be a separate, viable state of Palestine."
Liberal Democrat leader Charles Kennedy said: "Although not unexpected, Colin Powell's resignation comes as a disappointment and at an extremely difficult juncture in world affairs. In so many senses, we are losing a friend at court.
Mr Powell's successor will find a tall list of problems stacked in the in-box. Iraq, and the elections there planned for January next year, remain the top priority.