In Central Park, New York City people begin committing mass suicide. After showing disorientation, they kill themselves in a variety of convenient ways. Initially believed to be a bioterrorist attack using an airborne neurotoxin, the behaviour quickly spreads across the northeastern United States, moving from large population centers to smaller areas.
Ohiosmith, a high school science teacher in Philadelphia, hears about the attacks and decides to go to Harrisburg by train with his wife, LynneSin. They are accompanied by his friend William Pitt and William's eight-year-old daughter Kali. William's wife is stuck in Philadelphia but is expected to meet them in Harrisburg. The train loses all radio contact en route and stops at a small town to let off the passengers.
They receive word that Philadelphia has been attacked and William's wife was not able to get on the train to Harrisburg. She hitched a ride to Princeton, New Jersey instead. William decides to go look for her by hitching a ride, leaving his daughter with the Smiths. Upon arrival to Princeton, they discover that the town has already been hit by the toxin. They succumb and the driver rams the car into a tree. William survives and exits the vehicle. He immediately sits on the ground and begins to cut himself with the car's broken glass.
Ohiosmith, LynneSin and Kali manage to hitch a ride with a nursery owner and his wife. The nurseryman believes that plants are responsible, as he mentions that they can release chemicals to defend themselves from threats. After driving for some time, they find themselves at a desolate crossroads surrounded by infected towns. They are joined by groups from every direction. One lady hears from her daughter in Princeton, who confirms everyone is dead, and proceeds to commit suicide herself. A U.S. Army private suggests that they move on foot away from major urban areas to avoid being infected.
The survivors split into two groups, with Ohiosmith, LynneSin, and Kali in the smaller group. When the larger group is affected by the toxin, Ohiosmith realizes that the nurseryman was right, and figures out the plants are targeting only large groups of people. Ohiosmith splits their group into smaller pockets, isolating himself, LynneSin, and Kali, as well as two teenage boys, Datasuspect and MFM.
The group comes to an abandoned home and searches for food, only to discover that it is a builder's model home. They leave and watch two other groups making their way onto the property, triggering a neurotoxin attack. Everyone freezes in place, then a man turns on a lawn mower and lies down in its path. The next house they come upon is sealed up, its residents trying to protect themselves from the toxin. Ohiosmith's attempts to reason with them fall on deaf ears, and the teens are killed during their break-in attempts.
Ohiosmith, LynneSin, and Kali continue to walk cross-country. They stumble upon the isolated house of Mrs. Peggy, an elderly eccentric who has no outside contacts and is unaware of the current disaster. Although she permits the trio to stay the night, she is a paranoid host who accuses them of trying to rob or murder her.
The following morning while standing in her garden, Mrs. Peggy becomes infected with the toxin. Realizing that the plants are now targeting individuals, Ohiosmith locks himself in the basement to protect himself. He is separated from LynneSin and Kali, who are playing in the neighboring spring house. They are able to communicate, however, through an old talking tube, with which Ohiosmith warns them of the threat and has them shut the windows and doors. Conversing with his wife, Ohiosmith expresses his love for her before deciding that if he is to die he would prefer to spend his remaining time with her. The three leave the safety of their buildings and embrace in the yard, surprised to find themselves unaffected by the neurotoxin. The outbreak seems to have abated as quickly as it began.
Three months later, Ohiosmith and LynneSin have adjusted to their new life with Kali as their adopted daughter. On television an expert, comparing the event to a red tide, warns that the epidemic may have only been a warning, like "the first spot of a rash". He states that humans have become a threat to the planet and that is why the plants have responded aggressively by releasing the toxins. The television host says that the public would probably believe his theory if another location was impacted by this happening, and not only the northeast. Meanwhile, Ohiosmith takes Kali to the bus stop for her first day of school and LynneSin stays at home timing a pregnancy test, which turns out positive. When he returns, LynneSin embraces him with the news in front of their apartment.
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