After receiving a distress call from a science party on Camus II exploring the ruins of a dead civilization, the Enterprise rushes to assistance. All members of the party appear to be dead except the leader Dr. Janice Lester and the medical officer Dr. Arthur Coleman. Kirk and Lester had been in love in Starfleet Academy, but Lester's inability to rise to command status because of her gender led them to drift apart.
According to Dr. Coleman, Lester is suffering from some unknown sort of radiation poisoning. However, when the rest of the Enterprise landing party goes to aid a dying science party member and leaving Kirk and Lester alone, she activates an alien device she has discovered and exchanges bodies with Kirk. Lester is driven by jealousy and a persecution complex and complains to Kirk of the agony of being a woman. Now in the body of Kirk, she then tries to strangle Lester and kill the real Kirk. Kirk, McCoy, and Coleman return before she can finish, having been too late to save the scientist from selebium poisoning. Lester-as-Kirk orders everyone to be beamed about, and takes over the role of Kirk.
Aboard the Enterprise in secret consultation with Lester-as-Kirk, Dr. Coleman reveals that Dr. Lester deliberately sent the science team where she knew the selebium shielding was weak, and that she was supposed to kill Kirk during the interval provided by Coleman on the planet.
Lester-as-Kirk removes Bones as chief medical officer and installs Dr. Coleman, a former starship doctor who has been found incompetent by the Starfleet Surgeon General, in his place. Dr. Coleman attempts to prevent Kirk (in Dr. Lester's body) from interacting with the crew by sedating her, but she escapes to sickbay to talk to Bones and Spock. However, Lester-as-Kirk is there as well waiting for a physical examination ordered by McCoy. He proceeds to knock Kirk-as-Lester out and orders her be put in isolation and incommunicado.
Meanwhile, Lester-as-Kirk delays a rendezvous with the Potemkin to conduct gravitational studies of the Beta Aurigae binary system and insists that course be set for the Benicia colony, despite the fact that Starbase 2 is on the way and that Benecia possesses only primitive medical facilities.
Spock suspects something amiss, and goes to speak to (the real) Kirk in solitary confinement. At Kirk's request, Spock does a Vulcan mind probe and discovers the truth. Meanwhile, McCoy tests Lester-as-Kirk's dermaloptic reaction to color wavelengths using a Rubiana dermaloptic test to compare his basic emotional structure to previous results. Spock tries to escape with the real Kirk, but is stopped by Lester-as-Kirk and security guards.
This leads to a court martial trial for Spock. Spock puts Kirk (in Lester's body) on the stand and testifies that Kirk's mind is in actually in her body. Scotty talks to Bones in the hallway about the vote, and the conversation is recorded by Lester-as-Kirk. Lester-as-Kirk then orders the death penalty for Scotty, Bones, Lester (who is actually Kirk), and Spock, despite the fact that general order 4 is the only crime for which the death penalty is still in effect.
In the meantime, Sulu and Chekov refuse to obey Lester-as-Kirk's orders, and Kirk and Lester experience a temporary reversion of minds. In fact, to prevent reversion, Coleman informs Lester-as-Kirk that Lester must be killed. However, Coleman is too late carrying out the task, and Kirk's and Lester's minds revert to their appropriate bodies.