Those opposing Musharraf have seized on the unrest to press the president to give up his dual role as president and head of the military by the end of the year, when he is constitutionally obliged to.
When asked if he had talked with Musharraf about the removal of Chief Justice Iftikhar Muhammad Chaudhry, Negroponte said he had discussed the "general political situation" in Pakistan.
"It would be in the best interests of Pakistan for Musharraf to step down"
Jim ibarra, Cyberjaya, Malaysia
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Critics accuse Musharraf of suspending Chaudhry to remove obstacles to his re-election as president-in-uniform by the outgoing parliament, in defiance of the Pakistani constitution.
"I think this is something that President Musharraf himself is going to want to decide and this is a matter that is up to him," Negroponte said.
Richard Boucher, Negroponte's assistant, and Admiral William Fallon, the chief of the US central command covering Iraq and Afghanistan, also met Musharraf in an unprecedented trio of US official visits.
Musharraf suspended Chaudhry on March 9, leading to widespread protests and violence in Karachi in May which claimed 40 lives.
The visits follow intense pressure on Musharraf from Western allies with troops in Afghanistan to crack down on Taliban and al-Qaeda fighters allegedly holed up in Pakistan's northwestern tribal belt.
Musharraf seized power in a bloodless military coup in 1999.