The effect of nifedipine, one of the calcium channel antagonists, was examined in allergic and nonspecific reactions using rat skin and peritoneal mast cells. Rat passive cutaneous anaphylaxis response mediated by IgE antibody was inhibited by nifedipine (100 micrograms/rat) and also by cromolyn sodium (5 mg/rat). Skin reactions induced by histamine or methacholine were not inhibited, and skin reaction induced by serotonin was slightly inhibited by these drugs. The 45Ca uptake and histamine release in sensitized mast cells stimulated by ovalbumin were suppressed by nifedipine. In actively sensitized cells, nifedipine seems to be more effective on the inhibition of 45Ca uptake, but less effective on histamine release than cromolyn sodium. In mast cells, nonimmunologically stimulated by concanavalin A, compound 48/80, and calcium ionophore A23187, nifedipine exerted considerable inhibitory effects on both 45Ca and histamine release.