President Bill Clinton issued a statement deploring the attack which occurred as the three officials were on their way to work at the US consulate in the morning rush hour. As their van stopped at a traffic light, it was sprayed with gunfire by two assailants armed with AK-47 assault rifles.
"The attack on American personnel in Pakistan ... outrages all Americans," the President said, adding that he had ordered all US agencies to assist Pakistan in tracking down the killers. A planned visit to the country later this month by Hillary Clinton was expected to go ahead, however.
Among the possible motives for the attack was retribution by extremists for the arrest and extradition to America last month of Ramzi Yousef, who is awaiting trial in New York on charges of masterminding the 1993 World Trade Center bombing. He was captured after two years on the run.
Four others were convicted and jailed last year for the bombing, which killed six people and injured 1,000 others. Meanwhile, testimony is being heard now in the trial in New York of Sheikh Omar Abdel Rahman, accused with 10 others of attempting to launch a "war of urban terrorism" against America.
The US Secretary of State, Warren Christopher, who is on an eight-day tour of the Middle East, said the murders of the consular staff were "yet another reminder of the dangers we confront in the world-wide struggle against terrorism". He said the US, "will make available to the government of Pakistan, working in co-operation with them, any US resources that would assist in bringing those responsible to justice".
The Pakistani government has been striving to improve relations with the US. As well as co-operating with the snaring of Mr Yousef, it has recently approved the extradition of several suspected drug traffickers to the United States and is planning to send more. The Prime Minister, Benazir Bhutto, is due to make an official visit to Washington for talks with Mr Clinton next month.
Ms Bhutto sent a letter of regret to Mr Clinton, stating: "We condemn this heinous crime against innocent people which is part of a well-planned campaign of terrorism. Every effort will be made to apprehend the perpetrators."
Those killed were Jackie van Landingham, a secretary at the consulate, and Gary Durell, a communications director. The third passenger in the van, Mark McCloy, who worked in the consulate post-room, was injured and was reported in a stable condition.
While Mr Yousef is not expected in court in New York until next month, the trial of Sheikh Rahman and the other ten - described as the biggest terrorist trial in US history - took a critical turn this week with the first testimony by Emad Salem, a former Egyptian army officer, and FBI informant.
Mr Salem, who infiltrated the sheikh's inner circle in 1993 and taped hours of conversations related to the alleged conspiracies, is a vital witness for the prosecution. In the stand this week, however, he admitted to being a chronic liar, unable to resist making up stories about his past to convey the impression of being "a big shot".
Mr Salem, who had been paid more than $1m (£650,000) for his co-operation with the FBI, said he lied even to his former wife by claiming he had been a bodyguard to Anwar Sadat at the time of his assassination. He also conceded that he pretended to have known several other Middle Eastern leaders. "I told a lot of bragging stories," he said.
The admissions were drawn from Mr Salem by the prosecution in a tactical move to preempt the attempt that will inevitably be made by Sheikh Rahman's lawyers to discredit him as a witness.The 11 are accused of several intertwining conspiracies aimed at overthrowing the US government.