Human skin mast cell preparations were incubated with thiopental, thiamylal, methohexital, and pentobarbital in concentrations ranging from 10−5M to 10−3M. Both thiopental- and thiamylal-induced dose-related histamine release, with thiamylal having a significantly greater effect than thiopental (P< 0.05). In contrast, incubation of skin mast cell preparations with the same concentrations of pentobarbital and methohexital failed to increase histamine release above spontaneous levels at any concentration. The release of histamine by thiopental and thiamylal was not accompanied by the leakage of lactic dehydrogenase (LDH). Although a demonstration of histamine releasein vitrois not proof that clinical symptoms are causally related to histamine releasein vivo, methohexital may be preferred as the induction agent in patients showing extreme sensitivity to histamine (asthmatics) or increased histamine releasability (atopics).