The chemical form of mercury reactive by the histochemical technique was studied by using rats and mice treated with mercuric chloride (HgCl2) and methyl mercury chloride (MeHgCl). Mercury granules were demonstrated histochemically in the brain of HgCl2-treated rats with higher levels of inorganic mercury. However, mercury granules were not demonstrated in the brain of MeHgCl-treated rats in spite of a considerably high organic mercury level. In rats and mice with significant biotransformation of injected MeHg to inorganic mercury, the appearance of the peak inorganic mercury level and mercury granules in the brain seemed to occur on the same day. These results suggested that mercury granules in the brain represent inorganic mercury, but not organic mercury. In the brains showing mercury granules, the lowest level of inorganic mercury was 0.12 micrograms/g in HgCl2-treated rats, 0.14 micrograms/g in MeHgCl-treated rats, and 0.12 micrograms/g in MeHgCl-treated mice. These values were similar to the level of inorganic mercury in the brain from human autopsy cases. Mercury granules were demonstrated histochemically in nerve cells, choroid plexus and phagocytes in the brain of both HgCl2-and MeHgCl-treated rats, and in ependyma of MeHgCl-treated rats. The level of inorganic mercury of the brains showing mercury granules in phagocytes was lower in MeHgCl-treated rats than in HgCl2-treated rats. The numbers of mercury granules in nerve cells increased with the rising level of inorganic mercury in the brain of MeHgCl-treated rats.