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A police media spokeswoman said emergency services, including St John ambulance and volunteer firefighters, were called to a crash near Devil's Staircase at 1.37pm.
Two cars were involved - one appears badly damaged and has hit a rock wall, while another is against a barrier on the lake side of the highway.
St John communications adviser Chrissy Hamilton said one person is being flown to Dunedin Hospital with ''serious injuries'' and two other patients were transported to Lakes District Hospital by ambulance with minor injuries.
St John was notified at 1.31pm - two ambulances and helicopter were called to the scene.
An Otago Daily Times reporter at the scene says traffic was stopped in both directions, but one lane is now open.