A car left the road and ploughed into a group of youths on a Merthyr Tydfil housing estate.
Two boys, aged 12 and 10, were taken to hospital after the crash at Heol Scwrfa on the Gellideg Estate just before 7pm on Tuesday.
South Wales Police said that a silver Audi left the road and "collided with a number of youths at the location".
The air ambulance was sent to the scene and the two boys were taken to hospital.
A spokesman said that one of the boys suffered serious injuries and is being treated at the University Hospital of Wales, Cardiff.
He added: "The driver of the Audi motor vehicle is presently assisting police with the investigation."
The Welsh Ambulance said that one person was taken to hospital in Cardiff by air ambulance.
Police have thanked members of the public and local community who helped at the scene and "for their patience during the road the closure."
Local resident Peter Davies, 73, said: "Nothing like this has ever happened before.
"All the residents were out on the street and we knew it was serious when the air ambulance arrived. The children weren't in a good condition so I hope they’re okay."
One resident, who didn't want to be named, said: "I didn't see or hear it happen but I heard everyone running out to the street afterwards.
"It's so sad what has happened and I hope the children involved are OK."
Anyone who may have witnessed the incident, or the manner of driving of the vehicle prior to the collision, is asked to contact South Wales Police on 101 and quote Occurrence number 1900259687’
