The study was undertaken to examine the effect of isoprinosine treatment on in vitro histamine release from peritoneal mast cells. The experiments were done on mice which received isoprinosine orally, at a dose of 50 or 100 mg per kilogram of body weight per day, in divided doses, every 8 hours, for a period of 1 - 9 days. After isoprinosine treatment, there was a significant decrease of in vitro Con A-induced histamine release from mast cells. This inhibitory effect was observed in both tested groups. In the second experiment, with mice sensitized with egg albumin, the treatment with isoprinosine gave also a significant inhibition of anaphylactic histamine release from mast cells, as compared with that of control without isoprinosine treatment. Results of both experiments suggested that isoprinosine may have some inhibitory effect on mast cell activation.