In the quaint town of Pontypool, Ontario, a former shock jock turned radio announcer, Grant Mazzy, is on his daily commute through a heavy blizzard to the radio station. His journey takes an eerie turn when he encounters an underdressed woman on the road, who startles him by repeating his words before vanishing into the snowy chaos. Arriving at the station, Grant finds himself butting heads with station manager Sydney Briar and technical assistant Laurel-Ann Drummond as he tries to maintain his on-air persona amidst their growing frustrations.
As the morning unfolds, they receive an alarming report from a supposed helicopter reporter, Ken Loney. Initially believed to be a prank, Ken’s update reveals a terrifying scene of disorder and bloodshed surrounding the office of Dr. Mendez, leaving the crew questioning its legitimacy. After a series of disconnections during their attempts to verify this report, Ken finally calls back to relay cryptic messages about an “infected” young boy, whose nonsensical mumblings include only the word “Mommy.” Just then, a bizarre transmission interrupts: it’s a warning in garbled French advising everyone to stay indoors and avoid certain phrases, including terms of affection and conflicting statements. The unsettling news confirms that Pontypool is now under quarantine.
As the tension escalates, Ken once again manages to connect with the station, bringing with him the horrifying reality of the outbreak as he becomes infected, repeating the word "sample." Meanwhile, Laurel-Ann begins to exhibit bizarre and violent behavior, obsessively repeating the word “missing” and emulating a boiling kettle's sound. When Dr. Mendez arrives, he theorizes that a virus has somehow infiltrated human language itself, transmitting the infection through specific words. This revelation leads to chaos within the booth; as they desperately seek a solution, Laurel-Ann violently attacks the booth's window, ultimately succumbing to her own infection.
With the mob now breaking into the studio and the stakes rising, Sydney takes drastic action, broadcasting a loop of Grant declaring “Sydney Briar is alive” to distract the swarm outside. Dr. Mendez struggles with the affliction, discovering that the virus only targets the English language, while the others attempt to evade their pursuers by speaking French. As the dangers close in, Sydney feels the weight of guilt for her choices, caught in the throes of the infection when she starts repeating the word "kill." In a daring attempt to save her, Grant persuades her to reinterpret “kill” as “kiss,” leading to a moment of vulnerability as they share a kiss to dispel her symptoms.
Equipped with newfound strategies to combat the virus, Grant and Sydney take to the airwaves, wilfully spouting nonsensical phrases to aid their infected audience in defiance of authority. Just as the countdown from outside reaches its climax, they share another kiss in the sound booth, and the screen plunges into darkness with the credits rolling. The credits feature an ensemble of audio reports, indicating further outbreaks and hinting that the quarantine measures have failed. In a striking twist post-credits, the visual shifts to a stylized black-and-white rendition of Grant and Sydney, suggesting a radically different turn in their journey as Grant shares his plan to "get out of here," ultimately bursting into color, symbolizing hope amid chaos.
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