A police spokesman said they were called at 2.34pm to State Highway 8 between Lawrence and Beaumont, in Central Otago.
St John spokeswoman Chrissy Hamilton said three people suffered moderate injuries and another two sustained minor injuries, all have been transported to Dunedin Hospital by Otago Regional Rescue Helicopter.
One of the vehicles was reported to be a motorhome, the spokesman said.
''The caller said there were persons trapped.''
Fire and Emergency New Zealand Brent Dunn said at 3.10pm there were two people each trapped in a separate vehicle, just north of Lawrence.
One fire crew was working to free a person from one of the vehicles and there were ''multiple patients,'' requiring treatment, Mr Dunn said at the time.
Three more fire crews were on their way.
St John spokeswoman Chrissy Hamilton said two Otago Regional Rescue Helicopters and two ambulances were on scene.
