A St John spokeswoman said a rapid response vehicle, two ambulances and a manager responded to the scene and treated then transported two people in serious condition, to Hawke's Bay Hospital.
State Highway 5 between Napier and Taupō was also closed following a serious two-vehicle crash, involving a truck and a ute, on Tuesday morning.
Waka Kotahi confirmed through social media that SH5 had fully reopened by 11.45am.
A police statement said emergency services responded to a crash between the crossroads of High Level Rd and Wairango Rd, Iwitahi, which was reported to police just after 6am.
A St John spokeswoman said St John treated, and then transported two people in serious condition to Waikato Hospital by air ambulance.
The spokeswoman said two other people in moderate condition were treated, and then transported to a local medical facility by road ambulance.
A Te Whatu Ora– Health New Zealand, Waikato spokesman said both people are in stable condition in a ward of Waikato Hospital.
A police spokesman said another person was taken to hospital following a single vehicle incident on Mangatarata Road, near Waipukurau, at 11.51am on Tuesday morning.
The spokesman said the road was briefly closed but had since reopened.