A police spokeswoman said one person with serious injuries was flown to Dunedin Hospital by rescue helicopter after being freed from their vehicle at the collision near Henley.
St John spokeswoman Jess Miller said a further three people were in a moderate condition and another two had minor injuries. Three ambulances were attending and a rescue helicopter was on its way.
A police spokeswoman said the highway had now reopened after detours were put in place after the collision, which occurred on a long straight with a passing lane about 3.15pm.