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Late one afternoon in May 1967 three Missouri boys slipped through their backyards to do what they loved: explore a labyrinth of caves in Hannibal -- the hometown of Mark Twain -- as if they were re-enacting the adventures of Huckleberry Finn.

They were never seen again.

The unknown fate of the children -- Billy Hoag, 10, Joey Hoag, 13, and Craig Dowell, 14 -- is one of Hannibal's greatest mysteries, haunting residents of the small Mississippi River town for 50 years.

Did the boys die inside the sprawling underground Murphy's Cave where they were reportedly seen heading? Or were they met with a sinister fate?

An exhaustive search, which included spelunkers and FBI agents, yielded no clues.

"They disappeared without a trace," said 80-year-old Richard McHargue, who was a young local radio reporter when the boys disappeared.

"It was a traumatic experience for the locals here," McHargue said. "Even though this is the boyhood home of Mark Twain, we were not used to that kind of intense exposure."

"It took your breath away," he said.

On May 10, 1967, Joey Hoag stepped off the school bus outside his parents' home in Hannibal's Southside neighborhood where he was greeted by his 16-year-old sister, Debra "DeDe" Hoag. Billy was already inside the house, which he shared with his 10 siblings. Joey walked up to his bedroom and changed out of his school clothes.

The Hoag parents were shopping at a nearby meat market and DeDe was giving orders.

"I said, 'You stay in the yard now, you hear me?'" she recalled. "Billy didn’t answer."

The two brothers had ventured out the night before to the caves adjacent to Highway 79, which meandered through the land like the Mississippi River and which was under construction at the time. Workers were blasting through the earth as they built a new Route 79, leaving gaping holes in the hillside and exposing a network of passage ways leading into the caves.

"The night before, the boys had come home covered in red clay mud – they had been up on the road bed," DeDe told Fox News.

"Workers were blasting the old road and putting in a new one," she said. "Dad told them: 'Don’t you ever go into those holes again.'"

Whether the Hoag brothers and their neighborhood friend, Craig Dowell, entered Murphy's Cave is not known.

Witnesses reported seeing the trio walking in the direction of the cave, according to the Hannibal Courier-Post, and DeDe said flashlights and a homemade ladder were later found missing from the family home.

For the next 10 days, federal law enforcement and the national media descended upon Hannibal, a town of about 20,000 people at the time. Members from the National Speleological Society -- flown in from Washington on Presidential Jet 2 -- were also at the scene, according to archived reports from the Courier-Post.

Spelunkers made their way through Murphy's Cave, crawling through small spaces in the rock and mud looking for any sign of the boys.

"They mapped out that cave and they didn’t find anything," DeDe said.

The construction company, meanwhile, was immediately ordered by the mayor to keep the holes open, but workers sealed them only a few days after the disappearance, according to DeDe and her family.

"When they blasted those holes open, they didn’t put any kind of caution tape around them," DeDe said. "I think the boys got buried in one of the holes and I think someone from the construction company who ran the equipment knew that they had buried them."

With no sight of the boys in the caves, questions about their whereabouts grew even darker. Trains leaving Hannibal after 4:40 p.m. on May 10 were all searched for the boys, according to the Courier-Post. Speculation about a possible kidnapping spread throughout the town.

On May 12, the newspaper reported: "Mayor Harry Musgrove requested that the National Guard begin a search this morning from the Universal Atlas Cement Plant at Ilasco north along the river to a point beyond the cave area."

Missouri Lost Boys 2

The front page cover of the Hannibal Courier-Post on May 12, 1967. (Hannibal Courier-Post)

The paper also reported all kinds of tips: A lone sock thought to be Dowell's found in a quarry by members of the Mark Twain Emergency Squad and a red substance believed to be blood.

McHargue's son, Mike, was 8 years old when the boys disappeared. Now lieutenant of the Hannibal Police Department, the younger McHargue said, "It’s highly likely they got lost in a cave."

"They might have encountered a large pool of water down a slope," he said.

But, McHargue noted, "Under Missouri law, any missing person case is never closed. It stays open forever until it’s solved."

"Should we get a lead, we will investigate," he told Fox News.

For Dede Hoag, who lives three miles from the old caves, the anguish over her brothers soon turned into a chronic anxiety and claustrophobia she said she's lived with her entire adult life.

"When the boys disappeared, I couldn’t eat and I couldn’t sleep," she said. "I used to think, 'How can I eat when they’re not eating? How can I put a blanket on myself when they don't have one?'"

Billy, red-haired and freckle-faced, was mischievous and a "funny little thing," she said. Joey was more serious, a science student often seen with a telescope he used to watch the stars.

Their void, DeDe said, is felt always.

"There isn't a day that goes by that there isn't something that makes me think about them," she said.

Cristina Corbin is a Fox News reporter based in New York. Follow her on Twitter @CristinaCorbin