A 2-year feeding study of methylmercury chloride (MMC: 0, 0.4, 2, or 10 ppm) was conducted in B6C3F1 mice (60 mice of each sex/group) to compare chronic toxicity and carcinogenicity results with those for ICR mice from our previous study in which males of the 10-ppm group showed an increased incidence of renal tumors without any abnormal in-life parameters. In B6C3F1 mice of the 10-ppm group, neurotoxic signs characterized by posterior paralysis were observed in 33 males after 59 weeks and in 3 females after 80 weeks. In males, a marked increase in mortality and a remarkable decrease in body weight gain were observed after 60 weeks. Toxic encephalopathy consisting of neuronal necrosis of the brain and toxic peripheral sensory neuropathy were induced in both sexes in this group. Chronic nephropathy, testicular atrophy, and glandular stomach ulcer increased in incidence in the males; chronic nephropathy also increased in incidence in females. In proliferative lesions, there were significant increases in the incidence of renal adenoma and/or carcinoma (16/60) and tubular cell hyperplasia (14/60) in males of the 10-ppm group, as compared to the control group. The incidence of chronic nephropathy also increased in males of the 2-ppm group. The results of this study indicate that the susceptibility of B6C3F1 mice to renal toxicity and renal carcinogenicity is comparable to that of ICR mice, and B6C3F1 mice are more sensitive to the chronic neurotoxic effects of MMC than are ICR mice.