The US embassy in Nairobi said public landmarks in Kenya and Ethiopia could be targets for suicide bombers.
The alert follows the collapse of peace talks between rival factions in Somalia vying for control of the country.
In Somalia there are reports of heightened military preparations in an increasingly tense situation.
The BBC's East Africa correspondent, Adam Mynott, says the warning is in one respect specific - it talks of a threat of suicide explosions in prominent landmarks in Kenya and Ethiopia and warns US citizens to take caution in prominent public places.
However, prominent landmarks in Kenya and Ethiopia could mean a very extensive list of possible targets.
A spokeswoman at the US embassy in Nairobi said the warning was based on threats by Sheikh Hassan Dahir Aweys.
Sheikh Aweys is one of the leaders of a group of Islamic courts in Somalia who urge Somalis to carry out the attacks.
The Islamic courts are in a struggle for power in Somalia with the weak interim government of the country.
Talks in Sudan between the two sides intended to find a peaceful solution collapsed on Thursday.
Militias in Somalia are reported to be making preparations for conflict by reinforcing frontline positions and recruiting more fighters.