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Police were called to Streatham High Road junction with Mitcham Lane just before 6:30am this morning.
They found both a motorcyclist and a pedestrian, both thought to be in their thirties, suffering injuries.
Sadly the pedestrian died at the scene.
The motorcyclist has been taken to a South London hospital where he remains in a serious condition.
Motorists are advised to avoid the area as Streatham High Road will be closed to traffic for some time.
No arrests have been made.
Police are investigating.