Police officers said they were investigating how the bomber managed to breach strict security measures and walk into the offices of the World Food Program (WFP) and detonate about eight kilograms of explosives.
There was no immediate claim of responsibility, but the attack comes during an upsurge of suicide bombings in Pakistan as the new Taliban leadership vow to avenge the killing of their commander Baitullah Mehsud in a US missile strike.
"According to the latest reports, four people have been martyred - one of them is an Iraqi national. Six people have been injured, all of them are Pakistanis," Interior Minister Rehman Malik told reporters.
There were scenes of confusion around the WFP compound in central Islamabad, with smoke billowing out from behind the blast walls and ambulances rushing to the scene, where bloodied survivors were walking amid shattered glass.
Bani Amin, deputy inspector general of police operations, earlier confirmed that two Pakistani women and an Iraqi man were killed, and said the explosion was caused by a suicide bomber who entered the building on foot.
"We have recovered legs and the skull of the suicide bomber. We are investigating how he managed to enter inside the building. There are scanners, there are cameras, and strict security arrangements," Amin said.
The WFP confirmed in a statement from Rome that three of its staff members had died in the blast, with two UN employees still in a critical condition.
"It is a tragedy for WFP and for the whole humanitarian community in Pakistan," Amir Abdulla, the WFP's deputy director based in Rome, said in the statement.
"These people were working to help vulnerable people."
There was no immediate information available about the fourth fatality.
UN spokeswoman Ishrat Rizvi said that all the UN offices in the capital "have been closed for security reasons until further notice".
Prime Minister Yousuf Raza Gilani's office issued a statement saying he "strongly condemned" the blast and ordered an inquiry into the bombing.
There was no immediate claim of responsibility, but Taliban militants holed up in the northwest tribal belt have been blamed for a string of attacks and suicide blasts that have killed more than 2,100 people in the last two years.
Three bomb blasts in the past two-and-a-half weeks in the northwest have killed 28 people, with the Taliban claiming responsibility for one of the blasts and threatening to unleash bigger assaults.
There was a lull in bomb attacks after Baitullah Mehsud's death in an August 5 US drone strike, but analysts had warned that the new Taliban leadership would likely be keen to show their strength with fresh, dramatic strikes.
Security measures have been high in the capital, where the last blast hit on June 6, killing two policemen at their offices.
Source: The Australian