Multiple AbductionsSpender first came to the attention of Agent Mulder while proclaiming her belief that the aliens were coming to promote peace. At the time, Mulder was disillusioned by the revelations of Michael Kritschgau. He did not believe Cassandra's insistings that the aliens were calling her and other abductees to "lighthouses," where colonization would begin, despite a mass inceneration of abductees at Skyland Mountain, where Scully had been abducted three years earlier.
A rebel group of aliens who mutilated themselves to avoid infection by the black oil were attempting to destroy the work the Syndicate had done, finally summoning both Scully and Cassandra Spender to the same site in Pennsylvania. Before the rebels could manage to destroy the group, however, an alien craft appeared overhead and abducted Cassandra. (TXF: "Patient X", "The Red and the Black")
Alien-Human HybridCassandra later reappeared in a train car in Virginia, where doctors who had been operating on her were burned alive by the same faceless rebel aliens. She had been cured of her former disabilities, but now believed the aliens had far more sinister motives than she had originally thought, having learned of their plans for colonization. Demanding to see Agent Mulder, she explained her newfound concerns, then insisted that she be killed before everyone else died.
She was then taken by a decontamination team led by Diana Fowley for her presentation to the alien colonists. Before she could be presented, however, the site was overrun by alien rebels, who destroyed many of the key players of the Syndicate, as well as Cassandra herself. (TXF: "Two Fathers", "One Son")
After utilizing Nazi technology in transgenic implantation and UFO technology salvaged from the 1947 Roswell crash, humans in the Syndicate contacted the aliens to offer assistance in plans for colonization, what the Cigarette-Smoking Man called the "perfect conspiracy." They offered to develop a race of alien/human hybrids to assist in the colonization through their genetic work, which they soon realized would be a slave race. Members of the conspirators' families were given to the aliens in exchange for access to an alien fetus, which was kept in cryogenic storage (TXF: "The Erlenmeyer Flask"). The original exchange took place at El Rico Air Force Base in November of 1973. Many of the abductees were returned for subsequent testing, including Cassandra and Jeffrey Spender, and the reluctantly-included Samantha Mulder. With the genetic information obtained through these experiments, the Syndicate hoped to forestall the invasion while they worked slowly on the project, and, in secret, possibly develop a vaccine which would prevent the possession—or incubation—of victims infected by the alien virus.
Beginning with the 1973 abductions, Cassandra was taken many more times, each time being subjected to further and further tests, originally disabling and finally curing her. It was revealed that she was the primary test subject, and became, shortly before seeing her doctors attacked, the first successful living human to be hybridized with alien genetics. Upon learning of a successful hybrid, the colonists would have taken steps to eliminate the evidence of the project, but the gathering to present her to the colonists — a show of support that might buy slightly more time - was infiltrated by the faceless rebels, who destroyed Cassandra and the elders but failed to eliminate the Cigarette-Smoking Man or other factions of the Syndicate.