Previous experiments have shown that when14C‐histamine is incubated with human faeces, the radioactivity at times disappears from the fluid fraction. The present study describes a mechanism involved in histamine decay that might explain this phenomenon and that also might be operative in thein vivodetoxication of dietary histamine as well as of histamine formed in the lumen of the gastrointestinal tract. Freshly expelled human faeces were homogenized and incubated in a closed system at 38° in an atmosphere of N2with either ring‐labelled and unlabelled histamine or ring‐labelled and unlabelled N‐acetylhistamine.14CO2was collected on a paper cylinder moistened with NaOH. Considerable formation of14CO2from histamine was found in the faeces of 3 of 6 healthy subjects (15–42% recovered as CO2). These results demonstrate that the imidazole ring of histamine has been ruptured.14CO2formation from N‐acetylhistamine was demonstrated only in faecal samples with an inherent ability to form CO2from histamine. Since N‐acetylhistamine is deacetylated by human faeces, the formation of histamine may be an obligatory step in the ring rupture of N