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The front of the bus was destroyed by the force of the blast on the Aldwych near the Strand.
The bus had travelled over Waterloo Bridge along Lancaster Place and was passing a Ministry of Defence building and turning onto Aldwych when the bomb exploded.
The explosion comes just nine days after the IRA ended its ceasefire with a bombing in the Docklands area of London, which killed two people.
Scotland Yard says it received no warning of the explosion which happened at 2238GMT.
The blast, thought to have been on a New Cross to King's Cross bus, could be heard five miles (eight kilometres) away and witnesses described devastation at the scene.
Six people have been taken to St Thomas's Hospital. Three of the injured have "significant" head injuries.
A further two people have been taken to University College Hospital.
One man is "serious but stable" in intensive care while another was admitted with minor cuts.
Three of the casualties were in two cars in front of the bus when the explosion happened.
Paul Rowan, 31, a BBC employee, described how the bus was a tangled mess, with metal and glass scattered over about 50 yards.
"I saw one woman who looked in a very bad way. She was face down on the road with bad-looking head injuries. There was blood all over the place."
Ten ambulances, five fire engines and four paramedic units were called to the scene.
A large area of the Strand was cordoned off amid fears over another device and police with loudspeakers warned people to move away or to stay inside restaurants, theatres and hotels.
Charing Cross railway station was closed, preventing many people from catching their last trains home to south-east London and Kent.
No-one has admitted carrying out the attack but one theory is that the bomb exploded as it was being taken to another destination in London.
Detectives are sifting through the wreckage and the London Central bus company is to hand a tape from the video recorder fitted to the bus over to Scotland Yard for examination.
The Prime Minister John Major was being briefed by officials at 10 Downing Street about the attack. The Irish Government condemned the explosion as "an appalling outrage".
Irishman Brendan Woolhead, who suffered a fractured skull and pelvis in the explosion, was initially regarded as the prime suspect and placed under police guard in hospital.
Mr Woolhead's name was cleared but he died of an asthma attack in October 1996.
It later emerged that one person died in the explosion - IRA bomber Edward O'Brien. He was blown up and killed by his own device when it accidentally detonated.
Bob Newitt, 49, the bus driver hurt in the blast, suffered back and chest injuries while perforated eardrums have left him permanently deaf.
Several devices were found in the months after the bombing as the IRA launched a series of attacks on mainland Britain following the breakdown of a ceasefire.
On April 24, 32lb of semtex - the biggest bomb of its kind ever planted on the mainland - failed to explode on Hammersmith Bridge in west London.
On 15 June 1996, a massive bomb exploded in a busy shopping area in Manchester. Two hundred people were injured. Police believe the IRA planted the device.
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