When a Hirogen ship containing one erratic life sign is found adrift, Janeway sends an away team to investigate. They bring back a wounded Hirogen to sickbay and report that the species is obviously comprised of hunters. Skeletal remains found on the ship show that their entire existence is based on the hunt of prey as both food and prized possessions. Now, however, something is hunting them.

Insistent that he be returned to his ship, the Hirogen explains that he had just captured an alien when it broke free and attacked him. He is anxious to continue the hunt, and Janeway assures him that she beamed him to sickbay to treat his wounds. When Tuvok and Kim investigate structural damage to Voyager's hull, they find an intruder has entered the ship. A blood sample left at the scene shows it is a member of the highly dangerous Species 8472. The crew is put on intruder alert, but the alien has already entered engineering and attacks Torres.

The Hirogen informs Janeway that if he is not allowed to continue hunting the alien, he will tell his approaching ships to destroy Voyager. Knowing from their previous encounter that Species 8472 is susceptible to Borg nanoprobes, Tuvok and Seven of Nine load phasers with them and track the alien. They soon corner the wounded intruder and plan to stun him. When the Hirogen begins firing his weapon against orders, Tuvok turns his phaser on him.

Paris and Seven discover that Species 8472 boarded Voyager to attempt to open a singularity. Through telepathic contact with Tuvok, the alien explains that his ship was damaged during conflict with the Borg. He has been trapped alone, wounded and hunted by the Hirogen, and he just wants to get home. Although the Hirogen threatens that the crew will be slaughtered if the alien isn't surrendered to him, Janeway asks Seven to open a singularity. Seven refuses to help the alien escape and is confined to the cargo bay until the mission is over.

As the approaching ships fire on Voyager, forcefields go off-line and the Hirogen escapes from sickbay. When the alien becomes agitated, Janeway tells Seven to give it more Borg nanoprobes. As she complies, the Hirogen approaches and orders Seven to step aside, allowing him to continue his hunt of the prey. Just then, the alien breaks through the forcefield. As it struggles with the Hirogen, Seven taps into transport controls and beams them to one of the ships. The Hirogen immediately cease firing and leave the area at warp speed. As a consequence for her actions against the Captain's command, Seven's duties on Voyager are restricted.