The Piper PA31 was carrying a flight nurse, a transport medic and a patient about 360 miles from Crescent City, near the Oregon border, to Oakland when the pilot declared an emergency around 1 a.m.
The pilot planned to return to Crescent City but the plane vanished from radar 5 miles north of the Arcata-Eureka Airport on the far northern coast, Federal Aviation Administration spokesman Ian Gregor said.
Rescue teams led by the Humboldt County Sheriff's Department found the crash site hours later on land owned by a private timber company in the county about 280 miles north of San Francisco.
The county's chief deputy coroner, Ernie Stewart, said his office received four victims but he declined to identify them until next of kin were notified.
The plane was part of Cal-Ore Life Flight, which transports patients throughout Northern California and Oregon. Don Wharton, a spokesman for parent company REACH Air Medical Services, said nighttime flights are common.
The National Transportation and Safety Board will investigate the crash.