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As mast cell widely regarded as an important effector cells in the host response and can be considered as an exocrine unit having capacity to respond to a specific interaction on the membrane by secreting the contents of preformed granules containing biogenic amines, we studied rat peritoneal mast cell function under methylmercury (MeHg) influence both in vivo and in vitro. In experiments in vitro incubation of peritoneal mast cells with MeHg in the dose range 10-8 to 10-6 M did not induce mast cell degranulation, however modified the activation of mast cells by non-immunologic stimuli (the selective liberator of histamine, compound 48/80, and calcium ionophore A23187). We observed activation of stimulated secretion by preliminary incubation with low dose of MeHg 10-8 M and inhibition by dose of MeHg 10-6 M. In experiments in vivo we observed in mastocytes of rats treated with MeHg (40 μmol/kg per day x 5 days, p.o.) the suppression of calcium ionophore A23187- and compound 48/80 –induced histamine release 7 days, 15 days and 20 days after final administration. Simultaneously we found the significant increase of total Hg level in the mast cells following MeHg treatment of rats ( 5x10-5μg/103 mast cells). These results show that MeHg treatment can modify mast cell function in vivo and in vitro and provide insight into the understanding what role this cell has in the pathogenesis of Minamata disease.