The targeting of the American hotel chain was one of the largest terrorist attacks ever in Pakistan and came at a time of growing anger in Pakistan over a wave of cross-border strikes on militant bases by U.S. forces in Afghanistan.
A U.S. State Dept. official told CBS News correspondent Kimberly Dozier that a U.S. government employee was among the dead. Because of the "extent of the carnage, forensics will be required" to determine whether any more Americans were killed in the attack, the official said.
The five-story Marriott had been a favorite spot for foreigners as well as Pakistani politicians and business people to stay and socialize in Islamabad despite repeated militant attacks on it. The bomb went off close to 8 p.m., when four restaurants inside would have been packed with diners at the hour that Muslims break their daily fast during the holy month of Ramadan.
"I didn't understand what it was, but it was like the world is finished," said Mohammad Sultan, a hotel employee who was in the lobby when the bomb exploded.
It left a vast crater some 30 feet deep in front of the building, where rescuers ferried a stream of bloodied bodies. The fire was still burning more than six hours after the blast and had gutted the hotel, sending up a thick pall of smoke over the area. The death toll was likely to rise once the flames are extinguished and rescuers can thoroughly search the devastation.
The bombing came just hours after President Asif Ali Zardari made his first address to Parliament, less than a mile away from the hotel, and days ahead of the new leader's meeting with President Bush Tuesday in New York on the sidelines of the U.N. General Assembly.
Rehman Malik, the head of the Interior Ministry, told The Associated Press it was unclear who was behind the attack and there had been no claim of responsibility. But authorities had received intelligence that there might be militant activity linked to Zardari's address to Parliament and security had been tightened, he said.
Analysts said the attack is a warning from Islamic extremists to the new civilian leadership of Pakistan that it should end already-strained cooperation with the United States to pursue al Qaeda and Taliban militants entrenched in the lawless tribal region along the border with Afghanistan.
Zardari reappeared after midnight on state television to condemn the "cowardly attack." He said he understood the victims' pain because he had buried his own wife - assassinated former Prime Minister Benazir Bhutto - in December.
"Make this pain your strength," he said. "This is a menace, a cancer in Pakistan which we will eliminate. We will not be scared of these cowards," he said.
Pakistani security sources and the hotel's owner said the truck was being examined by security personnel immediately outside the gate when it detonated, reports CBS News correspondent Sheila MacVicar.
The explosion reverberated throughout Islamabad and shattered windows hundreds of yards away.
As survivors scrambled from the hotel a fire took hold and spread quickly, leading to fears that those injured by the blast might not escape the flames, reports MacVicar.
"The fire has eaten the entire building," said Mohammed Ali, an emergency service official at the scene. He said that after an initial chaotic search to find survivors, rescue teams had only been able to make two brief forays inside but found no bodies or survivors and had to retreat quickly.
Teams of firefighters sprayed water from firehoses as bulldozers cleared debris.
Earlier, a U.S. State Department official led three colleagues through the rubble from the charred building, one of them bleeding heavily from a wound on the side of his head. One of the four, who identified himself only as Tony, said they had been moving toward the rear of a Chinese restaurant inside the hotel after a first, small blast when a second explosion hurled them against the back wall.
"Then we saw a big truck coming to the gates," he said. "After that, it was just smoke and darkness."
Mohammed Asghar, a worker from a nearby office with a makeshift bandage round his head, said there was more than one man in the truck and that they had argued with the hotel guards.
"Then there was a flash of light, the truck caught fire and then exploded with an enormous bang," he said.
A U.S. security official told Dozier that the Marriott had "done everything U.S. officials had recommended they do" - to mitigate the risk of an attack, but this was always a possibility.
Because of that, U.S. citizens were always recommended to ask for rooms in the back of the building, away from the street, the official said.
Senior police official Asghar Raza Gardaizi estimated the truck carried more than 2,200 pounds of explosives. He said in the midst of the rescue operation that at least 40 people were killed and many more feared buried in the rubble.
However, Kamal Shah, a senior Interior Ministry official, said early Sunday he knew of only 38 confirmed deaths.
Associated Press reporters saw at least nine bodies scattered at the scene. Scores of people, including foreigners, were running out - some of them stained with blood.