Firefighters assisted police and ambulance staff.
An operational support unit remained at the scene to help with traffic management.
Hato Hone St John said it was notified at 3.53pm and responded with two ambulances, two operations managers, two helicopters and a rapid response unit.
Oturoa Rd north of Rotorua.
Two people with serious injuries were flown to Waikato Hospital.
Three others suffered minor injuries, with one taken by road to Rotorua Hospital, one flown to Waikato Hospital and one treated at the scene without requiring transport.
A spokesperson for Auckland Westpac Rescue Helicopters said its crew was tasked to Hamurana, Rotorua, alongside Tauranga Air 1 at 4pm to assist at a two-car motor vehicle accident.
“We are currently transporting two patients in a serious condition to Waikato Hospital.”