We investigated the properties of superoxide anion (O2-)-induced histamine release from rat peritoneal mast cells using superoxide anion radicals obtained from potassium superoxide (KO2). KO2 elicited a rapid histamine release in a dose-dependent fashion, without lactate dehydrogenase (LDH) release. The KO2-induced release was temperature- and energy-dependent. KO2 rapidly increased the intracellular free Ca2+ concentration, accompanied by a marked increase of Ca(2+)-uptake. These findings indicate that the increase in intracellular Ca2+ concentration is involved in the initiation of KO2-induced histamine release, and KO2 could be used as an agent of O2(-)-induced biological reactions.