Inhibitory effects of DSCG, tranilast, ketotifen, azelastine, antiallergic agents, and nicardipine, a calcium ion antagonist, on (45)Ca uptake and histamine release by rat peritoneal mast cells were examined when the cells were stimulated with antigen and com. 48/80. All of these agents inhibited both (45)Ca uptake and histamine release by mast cells stimulated with antigen in a dose-dependent manner. When the cells were stimulated with both antigen and phosphatidylserine (PS), inhibitory effects of DSCG and tranilast on (45)Ca uptake decreased, although effets of ketotifen and nicardipine were not affected by the addition of PS. Only the effect of DSCG on the release of histamine decreased in the experiments in which PS was added. When the cells were stimulated with com. 48/80, inhibitory effects of DSCG and tranilast on (45)Ca uptake and histamine release decreased, although the inhibitory effects of ketotifen and nicardipine did not decrease. The effects of the preincubation time with the agents on (45)Ca uptake and histamine release of mast cells were examined. The inhibitory effects of DSCG and tranilast were reduced by prolonged preincubation of mast cells with the agents. Tachyphylaxis to tranilast and to DSCG was observed, and cross tachyphylaxis between DSCG and tranilast was also observed.