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Nine people were injured and one is critically ill in hospital.
Emergency services were called at 8am today after reports of the crash on Wandsworth Road in Vauxhall.
Reports suggest there was one person, the pilot, on board the helicopter. London Fire Brigade said that two cars were also involved.
A motorist is in hospital after being rescued from a burning car by fire crews.
The helicopter hit a crane on top of St George Wharf tower, Britain’s tallest block of flats. One witness said it struck the side of the building as it fell to the ground.
Eight fire engines, four fire rescue units and around 60 firefighters attended with the police and ambulances.
Footage showed wreckage burning in the street on Wandsworth Road, which has been closed.
The aircraft involved is believed to be an Augusta 109 model.
A spokesman for London Mayor Boris Johnson said: “This is clearly a major incident involving considerable numbers of emergency service personnel.
“The Mayor’s thoughts are with the families of the two victims and with those injured.
“The Mayor has spoken with Met Police Commissioner Bernard Hogan Howe and Transport Commissioner Peter Hendy.”
“He remains in close touch with all his Commissioners and he will continue to monitor the situation closely.”
Witnesses described scenes of “absolute madness and fear”. They reported cars on fire and people screaming.
Newspaper distributor Raj Kumar, 28, said the crash occurred just before 8am.
He said “I saw the helicopter hit the crane and it took up to 30 seconds to come down from the building because it hit the sides.
“The force of the impact was so much that it caused the crane to bend. There were a lot of people coming out of the station who were in shock.”
Another witness described the crash as “a popping sound” followed by “rumbling”.
Mr Kumar added “the visibility was fairly good, the fog only came down later. The helicopter was white from what I remember, and it was travelling east, flying fairly low. I’ve seen It before, pretty much each day.”
Matt Haverson was doing construction work on railway arches near the incident. He said there was a good “pull together” with people attempting to extinguish small fires and escort other people away.
He told Sky News: “It was extremely scary… I obviously thought it was a terrorist attack.”
Witness Sarah-Beth Casey lives in an apartment near the incident.
She told Sky News: “You’re always worried about things like 9/11 and things like that. I have three small children with me in the flat. It’s one of your fears that something like this can happen.
“When I heard the explosion – it was like a little earthquake.”
She went on: “It was like a gas explosion. I looked up to see debris falling off the tower.”
She added: “I can’t see any people on the ground, it seems to be a lucky escape. The police and ambulance response was incredible.”
Commuter Sherna Noah described seeing a “large plume of dark grey smoke” as she crossed Battersea Bridge at around 8am.
She said: “I was coming across the bridge and basically I could see a few cyclists on the bridge looking towards the water.
“I looked over to see what they were looking at and could see a pall of grey smoke coming from the south side.
“You could see a large plume of dark grey smoke.”