Rat peritoneal mast cells, labelled with [C]arachidonic acid, released histamine and [C]arachidonic acid upon the addition of A23187. The release induced by low concentrations of A23187 was suppressed by removal of extracellular Na and by addition of the Na/H exchange inhibitor, amiloride. Addition of protein kinase C inhibitors resulted in only a modest decrease of [C]arachidonic acid and histamine release. [C]Arachidonic acid was hydrolyzed from both phosphatidylcholine and triacylglycerol. Amiloride inhibited only the hydrolysis from phosphatidylcholine. It is suggested that an Na/H exchange is stimulated secondary to an A23187-induced increase in intracellular calcium concentration. Increased Na/H exchange seems to facilitate the activation by intracellular calcium ions of phospholipase A as well as of histamine secretion.