Potassium chloride induced a dose-dependent release of histamine from rat peritoneal mast cells at concentrations from 5 to 150 mM in the absence of extracellular Ca2+. Potassium concentrations greater than 150 mM produced less histamine release. The release was energy-dependent and was complete within one minute. The histamine liberating effect of KCl could be inhibited by NaCl and by preincubation with ketotifen. The monovalent cations, Rb+ and Cs+ also evoked histamine release, whereas Na+ and Li+ were ineffective.