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While visiting London in 2004, he stepped off a curb, instinctively checking for traffic over his left shoulder. A speeding driver struck him from the right, killing Mack more or less instantly.

Mack concluded, "The furthest you can go at this point is to say there's an authentic mystery here. And that is, I think, as far as anyone ought to go."

By mid-December 1994, with Mack back in Cambridge, the Harvard committee accused him of failing to do systematic evaluations to rule out psychiatric disorders, putting “persistent pressure” on his experiencers to convince them they had actually been abducted by aliens, and preventing them from obtaining the help they really needed. As he wrote nearly a decade later in a manuscript he was seeking to publish as his masterwork, “When Worldviews Collide”: “I can see now that I had to a large extent created my problem with the literalness that I had treated the encounter phenomenon in the 1994 book. It is possible that in some cases people are taken bodily into spacecraft. However, the question is more subtle and complex.”

“I don’t even know. It just popped up in my head. He never said anything. He talked just with his eyes. It was just the face and the eyes. They looked horrible.”

“How did that get communicated to you?,” Mack asked.

The children told Mack and Callimanopulos on tape that the beings had large heads, two holes for nostrils, a slit for a mouth or no mouth at all, and long black hair, and were dressed in dark, single-piece suits. “I think it’s about something that’s going to happen,” said one little girl. “What I thought was maybe the world’s going to end. They were telling us the world’s going to end.”

Mack and his research partner Callimanopulos flew off to investigate a report that on September 14, 1994, a large, saucer-shaped spacecraft and several smaller craft had landed or hovered near a schoolyard in Ruwa, 40 miles northeast of Harare.

In 1994 BBC journalist Tim Leach called Mack’s office about a flurry of U.F.O. sightings in Zimbabwe.

“If what these abductees are saying is happening to them isn’t happening,” Mack demanded, “what is?”

His interest in the spiritual or transformational aspects of people's alien encounters, and his suggestion that the experience of alien contact itself may be more transcendent than physical in nature—yet nonetheless real—set him apart from many of his contemporaries, such as Budd Hopkins, who advocated the physical reality of aliens.

Only fairly recently in Western culture, notes Mack, have such visionary events been interpreted as aberrations or as mental illness. Mack suggested that abduction accounts might best be considered as part of this larger tradition of visionary encounters.

Mack noted that there was a worldwide history of visionary experiences, especially in pre-industrial societies. One example is the vision quest common to some Native American cultures.

Mack replied by saying "Face value I wouldn't say. I take them seriously. I don't have a way to account for them." Similarly, the BBC quoted Mack as saying, "I would never say, yes, there are aliens taking people. [but] I would say there is a compelling powerful phenomenon here that I can't account for in any other way, that's mysterious. Yet I can't know what it is but it seems to me that it invites a deeper, further inquiry."

Mack was somewhat more guarded in his investigations and interpretations of the abduction phenomenon than were earlier researchers. Literature professor Terry Matheson writes that "On balance, Mack does present as fair-minded an account as has been encountered to date, at least as these abduction narratives go." In a 1994 interview, Jeffrey Mishlove stated that Mack seemed "inclined to take these [abduction] reports at face value".

Mack concluded that the only phenomenon in psychiatry that adequately explained the patients' symptoms in several of the most compelling cases was post traumatic stress disorder. As he noted at the time, this would imply that the patient genuinely believed that the remembered frightening incident had really occurred.

His main contention for taking on what many consider to be “tabloid fare” was that the standard psychiatric “treatment” for people claiming alien abduction was to get them to deny that it ever happened. He argued that just because the experience falls outside a “mainstream” point of view, doesn’t mean that clinical professionals shouldn’t treat their patients with respect. He said that the closest comparable case a psychiatrist is likely to encounter would be a rape victim, and there is no shortage of agreement on how detrimental it would be to “treat” a rape victim by assuring the person they were never raped.

In June 1994 Harvard convened a confidential inquest under a former editor of The New England Journal of Medicine, Professor Emeritus Arnold Relman. “If these stories are believed as literal factual accounts,” Relman wrote Mack, “they would contradict virtually all of the basic laws of physics, chemistry and biology on which modern science depends.” Some went further, accusing Mack of ushering in a new dark age of superstition and magic.

Mack put it differently. “Every other culture in history except this one, in the history of the human race, has believed there were other entities, other intelligences in the universe,” he said. “Why are we so goofy about this? Why do we treat people like they’re crazy, humiliate them, if they’re experiencing some other intelligence?”

Undaunted, Mack appeared on The Oprah Winfrey Show with five of his lucid, articulate, and normal-acting abductees. “He believes them when they say they have been on the aliens’ spaceships,” declared Oprah. “And Dr. Mack believes them, he says, when they say that they have had children with aliens.”

A 37-year-old Boston writer intrigued him with a bizarre tale of being taken into a spaceship with Nikita Khrushchev and President John F. Kennedy during the Cuban missile crisis. Then, saying she was a double agent out to expose Mack’s U.F.O. cult, the woman, Donna Bassett, supplied tapes of her sessions to Time, which ambushed Mack with the hoax, calling him “The Man from Outer Space.” The Boston Globe followed up with a gleeful headline: ALIENS LAND AT HARVARD!

“These people are not lying and are not crazy. I know mental illness and this is not mental illness,” he said.

Two years after meeting Hopkins, Mack was working with dozens of experiencers, and one day he told incredulous fellow psychiatrists at Cambridge Hospital about alien abduction. He found that people from all over the world - who had never met each other – were telling the exact same abduction stories.

”Now everyone knows torture exists. That is accepted. But it is not accepted in our society that these UFO encounters exist. Therefore you need to have evidence of a pattern of such similarities that is showing up in hundreds, if not, thousands of cases. It is ironic that experiences like alien abduction encounters, UFOs, crop circles, and near-death experiences are called anomalies. In another words, in our culture, what lies outside the realm of the cultural agreement, about what is real, is called anomalous. Therefore a huge amount of human experience is called anomalous… scientific materialism does not give human beings any real satisfaction. It leaves us without spirit and it leaves us with an empty feeling because all it has to offer are more and more material things.”

It made him internationally famous and a regular guest on television talk shows. However, his emergence as a guru for UFO believers caused Harvard University acute embarrassment.

Mack spent five years interviewing more than 100 "experiencers" to produce his book Abduction - Human Encounters with Aliens and reached an astonishing conclusion: they were telling the truth. That is, they were not insane or deluded; in some unknown space/time dimension, something real had actually happened to them—not that Mack could explain just what or how.