Investigators say William Bradford Bishop, Jr brutally murdered his wife, mother and three sons aged 5, 10 and 14 at their home in Bethesda, Maryland, near Washington on March 1, 1976.
Dubbing him a "family annihilator," they say he was last seen a day later further south in North Carolina, where he is believed to have buried his victims' remains in a shallow grave and set them on fire.
Describing Bishop as a "highly intelligent" former State Department employee, the Federal Bureau of Investigation is offering a reward of up to $100,000 for information leading directly to his arrest.
"There is no indication that Bishop is dead," special agent Steve Vogt was quoted as saying on the FBI website.
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"If Bishop is living with a new identity, he's got to be somebody's next-door neighbor."
In the hopes of tracking down the now 77-year-old, the FBI has issued photos of an age-progressed bust, warning he could be hiding in plain sight.
"When Bishop took off in 1976, there was no social media, no 24-hour news cycle," Vogt said. "There was no sustained way to get his face out there like there is today. And the only way to catch this guy is through the public."
"Don't forget that five people were murdered," he said. "Bishop needs to be held accountable for that.