NBC News reported the Marines were killed when unexploded ordnance unexpectedly detonated, but the spokesman could not immediately confirm that, saying only the Marines had been clearing the area.
Marines spokesman Lieutenant Ryan Finnegan said the clearance operation would have involved anything necessary to keep the range free of obstructions, which could include disposing of ordnance. But he could not say they were handling ordnance when the accident occurred.
The cause of the accident, which happened on Wednesday morning at the Zulu Impact Area in the interior part of the base, was under investigation.
"We offer our heartfelt prayers and condolences to the families of the Marines lost today in this tragic accident," Brigadier General John Bullard, commanding general of the base, said in a statement. "Our first priority is to provide the families with the support they need during this difficult time."
The military did not release ages or other details about the four Marines killed.
Seven Marines were killed in an accidental munitions depot blast in Nevada in March. In May, a U.S. Navy SEAL was killed in a vehicle accident during a training exercise at Fort Knox in Kentucky.
In September 2011, two Marines aboard a helicopter died when it crashed during a training mission at Camp Pendleton, two months after a Marine was killed when another helicopter went down at the base.
Camp Pendleton, 40 miles (64 km) north of San Diego, is the main West Coast base for the Marine Corps.
(Reporting by Marty Graham in San Diego; Writing by Alex Dobuzinskis; Editing by Cynthia Johnston and Peter Cooney)