Someone called 911 shortly after 11 a.m. to report the collision about 30 miles north of Charleston near Lewisfield Planation in Berkeley County, county spokesman Michael Mule said. Federal Aviation Administration spokesman Jim Peters indicated the aircraft hit each other a little farther south, about 11 miles from Charleston.
The F-16 was on an instrument-training mission into Joint Base Charleston.
"All the facts at this point indicate that the pilot was talking to air traffic control ... when the accident occurred," said Col. Stephen Jost, commander of the 20th Fighter Wing at Shaw Air Force Base in Sumter, where the pilot is based.
An investigation is underway into the events leading up to the collision, including why the planes were so close to each other.
The F-16's pilot, Maj. Aaron Johnson, safely ejected, was picked up and transported to a hospital, authorities said.
"From what I understand, he seemed to be in pretty good shape," Berkeley County Rescue Squad Chief Bill Salisbury said.
The FAA identified the small private plane as a Cessna 150, which broke up considerably after the collision. No one on the ground was hurt by falling debris, which Berkeley County Sheriff Duane Lewis said fell largely in "a remote, marshy area."
The National Transportation Safety Board said two people aboard the Cessna died. They were not identified and the remains have not been found.
"We are in investigative mode trying to find out who that plane belonged to and who was on board," Salisbury told reporters. "... We have debris of the small plane scattered over a large area, and part of it is in a rice field."
Capt. Robert McCullough of the South Carolina Department of Natural Resources said at least part of the Cessna went into the Cooper River, while the F-16 crashed in Berkeley County. CNN affiliate WCBD
showed a picture of what appeared to be a jet engine lying next to a trailer in that area.
"The main object now is to locate the people and bring them back home to the families," Salisbury said.
At least 20 different agencies on the local, federal and state level are actively searching the crash site. The search area from where the crash occurred to where the military aircraft was found is 7.3 miles.