Pakistan has reacted angrily to the US army's top officer's suggestion that the government "sanctioned" the killing of journalist Saleem Shahzad.
Information minister Dr Firdous Ashiq Awan said that Adm Mike Mullen's statement was "extremely irresponsible and regrettable."
She said it would cause difficulties in relations between the sides and prove a setback to the war against terror.
US-Pakistan relations have been extremely fraught in recent months.
But Adm Mike Mullen's remarks are the most explicit yet in a downward spiral in recent US-Pakistan relations.
The BBC's Aleem Maqbool in Islamabad says that for a senior American official to say that he believes the authorities were involved heaps further pressure on Islamabad at a time when the Pakistani government's relationship with Washington - on which it has become so reliant for support - is under serious strain.
Mr Shahzad was kidnapped near his home in Islamabad in May. His body was found two days later in Punjab province. At the time, many in the Pakistani media blamed Pakistan's powerful military intelligence agency, the Inter-Services Intelligence (ISI), for the murder. The ISI has denied involvement in the case.
Adm Mullen said he could not confirm if the the ISI was involved.
"I have not seen anything that would disabuse that report that the government knew about this," Adm Mullen told journalists in Washington on Thursday.
"It was sanctioned by the government, yeah," he said.
Adm Mullen added that he did not have a "string of evidence" linking the death to the ISI.
Pakistan's ambassador to the US, Husain Haqqani, said an independent inquiry was evidence that the government was taking the journalist's killing seriously. The government-appointed commission to investigate the killing began work last month.
"Any evidence that our American friends have should be shared with that commission," Mr Haqqani told the New York Times newspaper.
"We are as interested in getting to the bottom of this matter as anyone else in the world, given our concern about human rights," he said.
Tension between the US and Pakistan hit a new low after the killing of al-Qaeda leader Osama Bin Laden by US commandos in the Pakistani city of Abbottabad.
Last month, Adm Mullen publicly acknowledged that there would be substantial cuts to US military numbers in Pakistan.
He said that US-Pakistan ties needed time to heal but added that it would be dangerous to abandon Islamabad.
"I think the worst thing we could do would be cut them off," he said. If that happened, he said, "10 years from now, 20 years from now, we go back and it's much more intense and it's much more dangerous."
Correspondents say that during his tenure, Adm Mullen has been a forceful advocate for maintaining dialogue with Pakistan and with its military establishment.
He was said to be close to the Pakistani army's chief of staff, Gen Ashfaq Kayani. Indeed, Adm Mullen is thought to have made more visits to Pakistan than any other senior US official or chief of staff in recent times. But, correspondents say, the latest comments are yet more evidence of his patience wearing thin.
He steps down as chairman of the Joint Chiefs of Staff later this year.
Mr Shahzad, who worked for the Hong Kong-based Asia Times Online and the Italian news agency Adnkronos International, had made a career writing about various Islamist militant networks operating in Pakistan.
Shortly before his death he had written an article about al-Qaeda infiltration in Pakistan's navy.
He reported that the militant group was behind a recent deadly assault on the Mehran base in Karachi because talks had failed over the release of several naval personnel arrested on suspicion of links to al-Qaeda affiliates.
Human rights groups have called Pakistan the most dangerous place in the world for journalists to operate, saying they were under threat from Islamist militants but also Pakistan's military and intelligence agencies.