Death may result from several pathologies that deviate from benign laughter.

Infarction of the pons and medulla oblongata in the brain may cause pathological laughter.

Laughter can cause atonia and collapse (”gelastic syncope“), which in turn can cause trauma. See also laughter-induced syncope and Bezold-Jarisch reflex.

Gelastic seizures can be due to focal lesions to the hypothalamus. Depending upon the size of the lesion, the emotional lability may be a sign of an acute condition, and not itself the cause of the fatality. Gelastic syncope has also been associated with the cerebellum.

• In the third century B.C., the Greek stoic philosopher Chrysippus died of laughter after giving his donkey wine, then seeing it attempt to feed on figs.
• Martin I of Aragon died from a lethal combination of indigestion and uncontrollable laughing in 1410.
• Pietro Aretino, who died in 1556, “is said to have died of suffocation from laughing too much.”
• It is said that the Burmese king Nanda Bayin in 1599 “laughed to death when informed by a visiting Italian merchant that Venice was a free state without a king.” This may be apocryphal, however, as Htin Aung states that the king abdicated a year before he was assassinated in 1600.
• In 1660, the Scottish aristocrat, polymath and first translator of Rabelais into English, Thomas Urquhart, is said to have died laughing upon hearing that Charles II had taken the throne.

• On 24 March 1975, Alex Mitchell, a 50-year-old bricklayer from King’s Lynn, England, died laughing while watching the “Kung Fu Kapers” episode of The Goodies, featuring a Scotsman in a kilt battling a vicious black pudding with his bagpipes. After twenty-five minutes of continuous laughter, Mitchell finally slumped on the sofa and died from heart failure. His widow later sent The Goodies a letter thanking them for making Mitchell’s final moments of life so pleasant.
• In 1989, a Danish audiologist, Ole Bentzen, died laughing while watching A Fish Called Wanda. His heart was estimated to have beaten at between 250 and 500 beats per minute, before he succumbed to cardiac arrest.
• In 2003, Damnoen Saen-um, a Thai ice cream salesman, is reported to have died while laughing in his sleep at the age of 52. His wife was unable to wake him, and he stopped breathing after two minutes of continuous laughter. He is believed to have died of either heart failure or asphyxiation.
  

• In the film Mary Poppins, the director of the bank at which George Banks works died of laughter.
• In the Monty Python sketch “The Funniest Joke In The World“, a joke is discovered (but never revealed to the viewer, other than a gibberish pseudo-translation into German) that causes people to die from laughter.
• In Who Framed Roger Rabbit, aside from The Dip (turpentine/acetone/benzine), too much laughter is one of the few things that can kill a cartoon character … or at least weasels.
• Batman’s archenemy, The Joker’s main weapon is “Joker venom“, a drug that will cause death from uncontrollable laughter.
• In the 1986 version of the film Little Shop of Horrors the sadistic dentist overdoses on laughing gas, causing him to laugh to death.
• In Ice Age 3, while searching for Sid, Manny, Diego, Crash, Eddie and Ellie cross the Chasm of Death, at the bottom of which are skeletons of dinosaurs who died laughing due to the mix of helium and nitrous oxide in the chasm.
• The post-punk band Killing Joke’s name is a direct reference to the concept of fatal hilarity and Monty Python’s Funniest Joke In The World.
• In the AdventureQuest online games by Artix Entertainment, there is a skeleton called Chuckles, said to have told a joke so funny that he died from laughter, and even continued to laugh (as an undead) after he died.
• In Gregor and the Curse of the Warmbloods, in a subterranean orchard called the Vineyard of Eyes, a certain carnivorous plant emits a gas that causes euphoria and laughter, rendering the victims defenseless to attacks by the plant.

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