Pakistan on Friday warned its cooperation in the US-led war on Al-Qaeda was at risk after heavily criticising the top US military officer for suggesting it could have approved a journalist's murder.
The row threatened to further strain relations already damaged by a covert American raid that killed Osama bin Laden two months ago and is the latest sign that cooperation in the war on Al-Qaeda and in neighbouring Afghanistan is at risk.
Pakistani journalist Saleem Shahzad's body was found just outside the capital Islamabad on May 31, bearing marks of torture.
He had complained of being threatened by the intelligence services and his colleagues believe that Inter-Services intelligence (ISI) was responsible for his disappearance, two days earlier, en route to a television studio.
On Monday, the New York Times quoted US officials as saying that the ISI ordered the killing to muzzle criticism after Shahzad wrote about links between rogue elements of the military and Al-Qaeda.
Admiral Mike Mullen waded into the fray on Thursday by saying: "I haven't seen anything that would disabuse that report" when asked about media reports that the Pakistani government approved Shahzad's killing.
Nevertheless, when asked if Pakistan's intelligence service had been involved, Mullen said he could not confirm the allegation.
Regardless, the remarks aggravated relations already strained by a covert US raid north of Islamabad in May that killed Al-Qaeda chief Osama bin Laden and the killing of two men by a CIA contractor in Lahore in January.
"If someone has given such a statement then it is extremely irresponsible," Pakistani Information Minister Firdous Ashiq Awan told a news conference.
"The statement by Admiral Mike Mullen regarding Pakistan will create problems and difficulties in the bilateral ties," she said.
"It will also impact our joint efforts in war against terrorism," added Awan, refusing to elaborate but saying the foreign ministry would issue another statement. The foreign ministry spokeswoman was not immediately reachable.
In the wake of the bin Laden raid, the United States recalled dozens of military trainers on Pakistan's orders and huge tensions remain over a covert American drone war against militants on the Afghan border.
Pakistan remains the main land route used by the United States to send supplies for the 150,000 foreign troops fighting in neighbouring Afghanistan.
Islamabad set up a judicial commission last month to investigate how the reporter died and the information ministry said such comments could be considered an attempt to influence the outcome of the inquiry.
"Some forces want to use this matter against the democratic government. Other than expressing regret, nothing more could be said about this statement," the information ministry said earlier in a statement.
The government last month gave a five-member panel six weeks to investigate the causes and circumstances of Shahzad's murder.
Mullen said he was "concerned" about the killing and suggested that other reporters had suffered a similar fate in the past.
"It's not a way to move ahead. It's a way to continue to quite frankly spiral in the wrong direction," said Mullen.
The ISI denied any involvement in murdering Shahzad, who worked for an Italian news agency and a Hong Kong-registered news site, despite widespread belief among his colleagues that intelligence agents had picked him up.
Pakistan's seemingly powerful military was humiliated by a unilateral American raid that found and killed bin Laden in the army town of Abbottabad on May 2, opening it up to allegations of complicity or incompetence.
On Thursday, Pakistan also denied a Washington Post report that the architect of its nuclear weapons programme claimed North Korea paid bribes to senior Pakistani military officials in return for nuclear secrets in the 1990s.
The Post said documents released by nuclear scientist Abdul Qadeer Khan purportedly show him helping to transfer more than $3 million to senior officers, who he says then approved the leak of nuclear know-how to Pyongyang.
The United States has long been concerned about Islamabad's nuclear arsenal despite insistence from Pakistan that the weapons are totally safe.