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Six people were killed when two cars collided on the M4 highway near the Blue Lagoon bridge, in Durban, early Saturday morning, provincial emergency medical services said.
"There were five occupants in one vehicle and one occupant in the other," said spokesman Caleb Wang.
"Both vehicles caught fire and the occupants of both vehicles lost their lives. The cause of the accident is now the subject of a police investigation."
The accident happened around 1.45am, he said.
Rescue Care spokesman Garrith Jamieson said it was believed a car was travelling on the wrong side of the highway when the accident happened.