The explosion happened on the bus at Lancaster Place, near the Strand, at 22.38pm. A London Transport spokesman said he believed the bus was a number 171 New Cross to King's Cross service.
The blast happened just nine days after the IRA's Docklands bomb, which killed two people, and three days after 11lb of Semtex explosive was found and defused in a telephone box in Charing Cross Road, the heart of London's theatreland.
With the crisis growing over the escalating level of violence started by the Docklands bomb, Scotland Yard said that it had received no warning before the bomb went off. Police at the scene were working on one theory that the bomber, presumed to be a member of the IRA, had accidentally blown up himself and the bus on the way to plant the device.
Early reaction suggested last night that the bomb had rocked remaining hopes of rebuilding an increasingly fragile peace process. John Taylor, the Ulster Unionist MP, said: "If people are letting off bombs in buses . . . then the peace process is over in the meantime."
Fears were also growing of a return to violence in Northern Ireland, with sources predicting that loyalist paramilitaries would no longer hold back.
Emergency services, including five fire engines and 10 ambulances, rushed to the incident last night, in which a taxi was also said to be involved. Witnesses said they saw shards of metal, which were all that remained of the bus's top floor, and that windows throughout the area had been blown in by the force of the explosion.
Rescue attempts were hampered by further, simultaneous reports of another suspect device planted nearby in Villiers Street, Charing Cross.
A taxi driver, John Jones, who was only 100 yards away from the blast scene, said the explosion appeared to come from the front of the bus, an old-style London Transport Routemaster. "There was like a dull thud and suddenly there was nothing left of the bus at all, just a skeleton. It all went up in smoke," he said.
"There were two people who I saw who looked badly injured and one of them was the bus driver, who was all covered in blood." He added: "Fortunately there weren't many people around at that time of night and most of the pubs were closed.
Mark Johnson, 25, was with friends in the Wellington pub, 100ft from the scene of the blast. He said: "We were standing in the upstairs of the pub having a beer with a group of friends when suddenly we heard a very loud bang. We all reacted very quickly. Many of the people in the pub dived to the floor.
"We went outside and saw that all the downstairs windows of the pub had been blown in. I saw a woman lying in the street and there was a great deal of debris and broken glass. The police arrived almost immediately.
"People rushed to help the injured woman. There were a number of other buses parked ahead and we were worried that there might be another bomb.
"That was a little too close for comfort," said Mr Johnson, a law student from Toronto, Canada : "I only flew into London on Friday."
Charles Schlumberger, a Swiss banker from UBS bank, said: "I was coming out of the Savoy crossing towards Waterloo Bridge when I saw the explosion about 100 metres ahead. I felt the shockwave from the blast and then there was a wall of debris, mainly glass, that started raining down in front of me. At first there was silence, some people fell to the ground straight away, others stood screaming."
"I saw one woman come out of the bus; she had a black coat on. I don't know if she was dead or badly injured. I saw three people running to help her."
Jonathan Bray, a homeless man who sleeps rough in Covent Garden, said: "The top of the bus folded in on itself. I saw one person on the floor, he was in a really bad way. The driver had been blown out of the bus. On the back of the bus there was a man holding a bag. He was burnt to a crisp."
One of the first on the scene was BBC radio reporter Paul Rowan, who said: "The entire bus seemed to be blown away. There was metal and glass for around 50 yards all over the place. I saw one woman who looked in a very bad way, she was face down on the road with bad-looking head injuries."
One witness, Anthony Yates, 26, said: "When the bomb went off, a taxi drove into the bus. The NatWest bank outside was badly hit."
Raymond Levy, a solicitor, was in his car only 30ft away from the blast. "I thought there was only the bus driver on board and when I got out of the car and got to the bus, he had got out but there were flames everywhere," he said. "The engine was still running and I was worried that the petrol would explode.
"With the help of a cab driver we undid the bonnet of the bus and turned the engine off. There were a few passers-by around and one woman was in shock and was running down the road screaming."
Scott Grover, 32, an American tourist from Boston, said: "The front of the bus was completely blown away but there didn't seem to be many people in it and I don't know how many were injured. There was debris everywhere."
London Ambulance said that six injured people - five men and one woman - were admitted to St Thomas's Hospital last night. Two people were reported to have been taken to University College Hospital. One middle-aged man was in intensive care with chest injuries, in a "serious but stable" condition, a spokesman said.