Lt. Reed (Dominic Keating) and Ensign Mayweather (Anthony Montgomery) discuss the triviality of chess while playing the game at a quick speed. The scene takes a macabre turn when it becomes apparent that they were serving as host bodies to two alien entities, and the topic of conversation shifts to that of an imminent danger, one which seems to have been encountered by other spacefarers and that "someone always dies."
A viral infection hits Commander Tucker (Connor Trinneer) while on an away mission with Ensign Sato (Linda Park) in the shuttlepod and he collapses while coughing heavily. Soon, Sato begins to exhibit the same symptoms. Upon examination by the ship's medical officer, Dr. Phlox (John Billingsley), it is found that the virus is highly contagious and is a silicon-based life form, rather than a carbon-based one. Captain Archer (Scott Bakula) explains to Tucker that Commander T'Pol (Jolene Blalock) and Phlox are looking for a cure, taking care not to mention that they were estimated to die within mere hours, given the rate of viral growth. Tucker realises the futility of the situation however, since it is basic knowledge that the human immune system is not adapted to fight a silicon-based virus.(For the same reason a silicon based virus wouldn't be able to infect humans since materials needed for replication are absent.)
The aliens, still residing within the bodies of Reed and Mayweather continue their observation of the human response to this unknown virus. From their conversation, it is understood that the non-corporeal aliens are members of an advanced species who are looking to make "first contact" with other species that have reached a certain level of advancement. A species' response to the unknown virus serves as a standardised test of intelligence. So far, within the 10,000 years of their observation, no species has yet been deemed worthy of first contact. As observers, they are neither responsible for the introduction of the virus, nor are they prepared to save anyone unfortunate enough to become exposed to it. The outcome is always one of two possibilities: Either the virus spreads until the entire crew dies, or those who are exposed to the virus will be isolated or killed to control the spread of the disease, as in the case of a recent Klingon encounter. Initially, the aliens chose Reed and Mayweather as host bodies as they were always present on the bridge and would be kept well informed, and their position as the armoury officer and the helmsman respectively would not interfere with the unfolding events of a medical situation. However, when they failed in their attempts to extract information through casual conversations with Tucker, Phlox and Archer, they decided to gain the information first hand by temporarily shifting to the bodies of Phlox and T'Pol.
To keep each other's spirits up, Tucker and Sato take the time to learn more about each other. Sato recounts how during her Starfleet training, she broke a commander's arm after he caught her running poker games on weekends, and was thrown out. However, in light of her exceptional linguistic skills, which was rare and in high demand, Starfleet looked the other way and she was reinstated into Starfleet. Later Sato becomes delirious and uses her code breaking skills to break out of the decontamination chamber, thus threatening the rest of the ship with a release of the virus. Archer successfully seals off the entire section, while Sato deliriously sets about trying to open the airlock. Tucker manages to calm her down and return her to the decontamination chamber whereupon Phlox instructs Tucker to administer a knock-out sedative to Sato and then to himself as a matter of precaution.
There is a noticeable difference in opinion between the two aliens. The more senior of the two seems determined to follow their protocol of non-interference and hence allow Tucker and Sato to die despite the fact that they could be saved. Conversely, the other alien sees something unique about the human species and feels the protocol is outdated and inhumane. As it is difficult to debate such topics on the bridge, the aliens decide to seek privacy in the decontamination chamber by invading what they thought were the merely sleeping bodies of Tucker and Sato. As Tucker and Sato are supposedly under heavy sedation, Phlox, via a video link in the sickbay, is shocked to see them up and talking profusely. Listening in on their conversation and performing a comparison of their brain wave patterns against their base references confirms Phlox's fears. The aliens, realising that their identity has been compromised, presumable through their sense of telepathy, approach Phlox while inhabiting Archer and T'Pol. They question Phlox to determine how their cover was blown and when satisfied, destroy the incriminating evidence and wipe Phlox's memory of the events, but not before Phlox gave them a piece of his mind.
Ultimately, Phlox and T'Pol find a possible way to disrupt the mechanism of the virus through the use of a narrow-frequency band of radiation, one which is detrimental to the virus, but not lethal to humans. The operation would need to be carried out in the medical scanner of the sickbay. Having extended the quarantine area and put on environmental suits, Archer and Phlox carry Tucker and Sato, who has begun to go into shock, to the sickbay. On arrival, Sato has lost vital signs and Phlox struggles to load an intra-cardiac syringe while in his bulky gloves. In desperation, he attempts to remove his gloves, but is stopped by Archer who reminds Phlox that the ship will need its doctor. Taking a risk that the cure devised will work, Archer takes off his gloves to load the injection and proceeds to thump the syringe into Sato's heart to deliver a form of adrenaline. This act of selflessness seems to capture the aliens' interest. A future form of the defibrillator is used in what proves to be a futile attempt to resuscitate Sato. Placing a sheet over the dead Sato, the pair work with renewed urgency to save Tucker. They place him into the medical scanner and administer a dose of radiation, balanced to target the viral cells without becoming lethal to the host. However, all is in vain as it becomes apparent that the radiation is ineffective against the virus, at least in vivo and at the dosage prescribed.
With Archer now exposed to the virus, Phlox has only a matter of hours to work on alternatives. He leaves to work from the bridge, in order to minimize the chances of accidental exposure to the virus, leaving Archer alone with a dying Tucker and a dead Sato. Suddenly, Tucker awakens and conveys his respect for Archer for his act of heroism. Sato also sits up and rebukes Tucker for breaking the protocol. The aliens, having given themselves away, now explain the situation to Archer, who is furious and makes an impassioned speech. The aliens become convinced that humans are worthy candidates for first contact. They save Tucker, Sato and Archer, but wipe the memory of the encounter from them all. With a warning beacon now in place to caution others of the biohazard, the site can no longer serve as a testing ground for the aliens. In the concluding scene, the aliens, again in the bodies of Reed and Mayweather, agree to start working on their proposal for formal first contact with humanity, a process that would take approximately 5,000 years, a short time for the long lived aliens. (Actual first contact with these aliens – the Organians – would occur about a century later, during the events of the original series episode "Errand of Mercy".)