"If he thinks he's going to solve problems by running for re-election, I can say to him, I think that certainly this war will not end as long as that's the case that he's there," Kerry said after talks with Arab League officials in Paris.
His comments came as Assad told Lebanese television he did not see "any reason" why he should not run in the next election.
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"I don't know anybody who believes the opposition will ever consent to Bashar al-Assad being part of the government," Kerry said.
"He has bombed and gassed people in his country... How can that man claim to rule under any legitimacy in the future?"
Ahead of talks between Western and Arab powers and the opposition in London on Tuesday, Kerry said Washington would continue to support moderate elements among those opposed to the regime.
"We are focused on assisting the moderate opposition," he said. "We will continue... Because we believe you need to get to negotiations.
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