Jared Chirp scans a medical test report and, disgusted, throws it in the trash. He hurriedly packs a suitcase while mumbling some religious prayers. An unseen figure watches through the window as the rain crashes outside the home in McMinn County, Tennessee. Jared grabs one last item — a revolver — and runs through the storm to his car. Once inside the car he drops his keys, and as he reaches for them on the floor, he sees a rattlesnake hissing. He grabs the gun, but a second rattlesnake comes into view. Suddenly Jared is swarmed by dozens of snakes. He fires into the pile with all six shots. The snakes attack and kill him.

In his office, Mulder reads from the report about the 116 separate bite marks from 50 different snakes. Although Jared's car was locked, there was no trace of snakes. He informs Scully that rattlesnakes usually hibernate in the winter. She notes that serpents are symbolic of religion. They travel to the Blessing Community Church in Tennessee to talk with Reverend Mackey about Jared's death. Jared's pregnant girlfriend Gracie overhears the conversation. Mackey has misgivings about the tragedy, and points them in the direction of Jared and Gracie's former church. This denomination practices snake handling. He names Reverend Enoch O'Connor as the prime source of animus toward the couple. O'Connor's Church of Signs and Wonders is an old, run-down shack with no lights. The agents are trying to find their way around in the dark and are startled to see snakes loose in the building. Before they can move, O'Connor turns on the lights to reveal not one, but many snakes on the church floor. He calmly stuffs them into a burlap sack as he tells Mulder and Scully that the death was a test of Jared's faith.

Iris, a volunteer at Mackey's church and the owner of the boarding house where Gracie is living, tells Mackey that Jared called the night he died looking for Gracie. She had kept this a secret. Mackey reassures her that he will help her deal with this later, and Iris goes into an office to work on church bulletins. Suddenly, her staple remover turns into a snake head and bites her hand. She washes the wound in the bathroom sink and notices snakes slithering from out of nowhere. She screams. Later, Iris' body is removed as Mulder and Scully talk to Mackey. He tells them that Jared called the boarding house looking for Gracie and mentioned something about paying for his sins. They question Gracie, but she does not believe O'Connor was responsible for the murders because he is her father. When she became pregnant, O'Connor kicked her out of the house and the church. Mulder and Scully return to Signs and Wonders and split up to investigate. Scully enters a room with snakes and O'Connor appears. He forces her hand into a box of serpents, preaching that she must be judged by God. Before a snake reaches her, Mulder crashes in with his pistol raised. O'Connor is arrested. He tells Mulder that Satan is near. In his jail cell that evening, O'Connor kneels down to pray. Dozens of snakes slide into the cell between the bars.

Reverend O'Connor lies in an ICU hospital bed with serious snake bites. Yet Gracie has forbid any anti-venom medicine to be given to him on the basis of religious grounds. Scully speculates that perhaps Gracie is the killer. The agents comb Jared's room and find the medical report. Jared could not have been the father of Gracie's child because he was sterile. They wonder if Jared was killed because he learned the truth. In the hospital, Mackey convinces Gracie to rely on medicine to save her father. He leaves her alone with the unconscious O'Connor. Mulder and Scully arrive to find that O'Connor has escaped with Gracie. Mackey tells them that O'Connor fathered Gracie's baby, and this was the reason she wanted to leave her father's snake church.

Late that night, O'Connor brings Gracie to his church where the other members of the congregation are waiting. She struggles, but they manage to hold her down. O'Connor tells her to "resist the Devil and he will flee." Gracie's pregnant belly squirms and she miraculously delivers baby rattlesnakes instead of a child. O'Connor and the others are shocked. The next morning, Mulder and Scully arrive at the Church of Signs and Wonders as Gracie is being put into an ambulance. She is in deep shock and suffers from loss of blood, but there was no baby found with her. O'Connor has also disappeared. They see the snake tracks in the amniotic fluid, and an elderly woman in the church says that the "Devil was cast out." Scully gets in the ambulance and Mulder goes to rescue Mackey from O'Connor.

O'Connor confronts Mackey with a knife, but Mulder bursts in and fires at O'Connor. In the ambulance, Gracie tells Scully that her father did not harm her. He was the one who saved her. Meanwhile, O'Connor lies bleeding on the floor. He tells Mulder that he does not realize which side he is on, and, as he points to Mulder's heart, says to be "smart down here." Mulder considers this and approaches Mackey in the outer church office. Mulder accuses Mackey of being the father of Gracie's child and wanting to destroy O'Connor. He draws his weapon, but Mackey asks if Mulder would do well if put to the test. Snakes suddenly appear and swarm Mulder. He falls to the ground as they crawl in his clothes and bite him. Scully hurries to the church and hears Mulder cry out. She breaks down the door just as the last snake escapes. Later at the hospital, Mulder recuperates as Scully reports that police have not yet found Reverend Mackey.

At a church in Connecticut, a woman welcomes a Reverend Wells to the parish. Wells is really Reverend Mackey. He pulls out a mouse from the desk drawer. He opens his mouth as if to put it in, but a snake rises out of Mackey's mouth. The snake swallows the mouse in a single gulp and slips back inside Mackey's throat.