Histamine poisoning can result from the ingestion of food containing unusually high levels of histamine. Fish are most commonly involved in incidents of histamine poisoning, although cheese has also been implicated on occasion. The historic involvement of tuna and mackerel in histamine poisoning led to the longtime usage of the term, scombroid fish poisoning, to describe this food-borne illness. Histamine poisoning is characterized by a short incubation period, a short duration, and symptoms resembling those associated with allergic reactions. The evidence supporting the role of histamine as the causative agent is compelling. The efficacy of antihistamine therapy, the allergic-like symptomology, and the finding of high levels of histamine in the implicated food suggest strongly that histamine is the causative agent. However, histamine ingested with spoiled fish appears to be much more toxic than histamine ingested in an aqueous solution. The presence of potentiators of histamine toxicity in the spoiled fish may account for this difference in toxicity. Several potentiators including other putrefactive amines such as putrescine and cadaverine have been identified. Pharmacologic potentiators may also exist; aminoguanidine and isoniazid are examples. The mechanism of action of these potentiators appears to be the inhibition of intestinal histamine-metabolizing enzymes. This enzyme inhibition causes a decrease in histamine detoxification in the intestinal mucosa and results in increased intestinal uptake and urinary excretion of unmetabolized histamine.