Coniine is a poisonous chemical compound, an alkaloid present in and isolable from poison hemlock (Conium maculatum), where its presence has been a source of significant economic, medical, and historico-cultural interest; coniine is also produced by the yellow pitcher plant (Sarracenia flava), and fool's parsley (Aethusa cynapium). Its ingestion and extended exposure are toxic to humans and all classes of livestock; its mechanism of poisoning involves disruption of the central nervous system, with death caused by respiratory paralysis. The biosynthesis of coniine contains as its penultimate step the non-enzymatic cyclisation of 5-oxooctylamine to γ-coniceine, a Schiff base differing from coniine only by its carbon-nitrogen double bond in the ring. This pathway results in natural coniine that is a mixture—a racemate—composed of two enantiomers, the stereoisomers (S)-(+)-coniine and (R)-(−)-coniine, depending on the direction taken by the chain that branches from the ring. Both enantiomers are toxic, with the (R)-enantiomer being the more biologically active and toxic of the two in general. Coniine holds a place in organic chemistry history as being the first of the important class of alkaloids to be synthesized, by Albert Ladenburg in 1886, and it has been synthesized in the laboratory in a number of unique ways through to modern times.

Hemlock poisoning has been a periodic human concern, a regular veterinary concern, and has had significant occurrences in human and cultural history. Notably, in 399 BC, Socrates was sentenced to death by drinking a coniine-containing mixture of poison hemlock.

Poison hemlock (Conium maculatum) contains highly toxic amounts of coniine. Its presence on farmland is an issue for livestock farmers because animals will eat it if they are not well fed or the hemlock is mixed in with pasture grass. The coniine is present in Conium maculatum as a mixture of the R-(−)- and S-(+)-enantiomers.

Coniine is also found in Sarracenia flava, the yellow pitcher plant. The yellow pitcher plant is a carnivorous plant endemic to the southeastern United States. The plant uses a mixture of sugar and coniine to simultaneously attract and poison insects, which then fall into a digestive tube. Coniine is also found in Aethusa cynapium, commonly known as fool's parsley.

The history of coniine is understandably tied to the poison hemlock plant, since the natural product was not synthesizable until the 1880s. Jews in the Middle East were poisoned by coniine after consuming quail in the area that usually ate hemlock seeds, and Greeks on the island of Lesbos who also consumed quail suffered from the same poisoning, causing myoglobinuria and acute kidney injury. The most famous hemlock poisoning occurred in 399 BCE, when the philosopher Socrates is believed to have consumed a liquid infused with hemlock to carry out his death sentence, having been convicted of impiety toward the gods, and the corruption of youth. Hemlock juice was often used to execute criminals in ancient Greece.

Hemlock has had a limited medical use throughout history. The Greeks used it not just as capital punishment, but also as an antispasmodic and treatment for arthritis. Books from the 10th century attest to medical use by the Anglo-Saxons. In the Middle Ages it was believed that hemlock could be used to cure rabies; in later European times it came to be associated with flying ointments in witchcraft. Native Americans used hemlock extract as arrow poison.

Yellow pitcher plant, or Sarracenia flava, contains coniine. Aethusa cynapium contains cynopine, which is similar to coniine.

The (R)-(−) enantiomer of coniine is the more biologically active, at least in one system (TE-671 cells expressing human fetal nicotinic neuromuscular receptors), and in mouse bioassay, the same enantiomer and the racemic mixture are about two-fold more toxic than the (S)-(+) enantiomer (see below).