The histamine metabolite tele-methylhistamine (t-MH) was identified and measured in crude and purified peritoneal mast cells (MCs). Peritoneal dialysates, peritoneal cells, and purified MCs all contained t-MH in concentrations representing about 0.2% of the corresponding histamine (HA) levels. T-MH levels in crude cells represented about 70% of the total dialysate levels, indicating the presence of extracellular as well as intracellular t-MH. T-MH levels per MC in purified fractions were similar to those of crude fractions, indicating a MC origin for the intracellular t-MH. Histamine methyltransferase activity was not detected in crude or purified MC fractions, and incubations with the monoamine oxidase inhibitor pargyline failed to increase the content or release of t-MH in either fraction, suggesting a very slow or non-existent histamine methylation in MCs. Compound 48/80 produced a temperature-dependent release of HA and t-MH in crude and purified preparations, and Triton X-100 also released both amines. In all cases, the degree of release of both amines was correlated, consistent with a granular origin for t-MH in MCs. The low concentrations of t-MH in MCs do not necessarily indicate a role for MCs in HA metabolism, but suggest that t-MH may be a valuable marker for non-MC HA.