The US national security adviser has told the BBC that Washington needs guarantees from Pakistan that its nuclear arsenal is safe from militants.
General James Jones said Pakistan's army had repeatedly told him the stockpile was "under control", but "this is very much an ongoing topic".
The Pakistani government is fighting to stop Taleban militants expanding their power in the north-west of the country.
Pakistani President Asif Ali Zardari is due to meet Barack Obama this week.
Taleban threat
In an interview with the BBC's North America editor, Justin Webb, Gen Jones said that "things are moving in a more positive direction" in Pakistan, but that more assurances were needed about the safety of the country's nuclear weapons.
"If Pakistan doesn't continue in the direction that it presently is and we're not successful there then, obviously, the nuclear question comes into view."
"We have received many assurances from the military that this is something they have under control but this is very much an ongoing topic," he added.
"The world would like to know that on this question, that there's absolute security and transparency."
The safety of Pakistan's nuclear arsenal has become more of a concern to the US government since Taleban fighters began expanding their influence in northern Pakistan beyond the Swat valley, which they already largely control.
The Pakistani military has been engaged in an offensive to remove Taleban insurgents from the Lower Dir and Buner regions, parts of which are just 100km (60 miles) from Pakistan's capital, Islamabad.
Pakistan's nuclear weapons falling into the hands of the Taleban would be "the very very worst case scenario," said Gen Jones.
"We're going to do anything we can within the construct of our bilateral relations and multilateral relations to make sure that doesn't happen."
On the subject of Iran, Gen Jones warned that the US would not "wait forever" for Iran to respond positively to President Obama's attempt to improve US relations with the country.
"We're interested in getting this new relationship established, to the extent that there is going to be one, but it takes two - and we're still waiting for the appropriate response from the Iranians," he said.
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