Methoxychlor is carcinogenic for the liver of C3H and BALB/c mice and Osborne-Mendel rats, and possibly for the liver of dogs. Methoxychlor is also carcinogenic for the testis of BALB/c male mice, bone of B6C3F1 female mice, and the ovary of Osborne-Mendel female rats. The incidences of carcinomas of the liver were increased in C3H male mice and BALB/c male and female mice fed methoxychlor. There also was an increase in malignant neoplasms at all sites in BALB/c male and female mice. C3H and BALB/c male mice were more susceptible to the carcinogenic effects of methoxychlor than were female mice. BALB/c mice were more susceptible than C3H mice. Osborne-Mendel male and female rats developed significant incidences of carcinomas of the liver. The incidence of sarcomas of the spleen and abdomen, mostly hemangiosarcomas, was increased in male rats. Neoplasms of the pituitary, adrenals, and mammary gland were also increased in methoxychlor-treated female rats. Miniature swine given methoxychlor developed chronic renal disease in relatively short periods of time. There also was hyperplasia of the mammary gland and uterus, suggesting an estrogen-like effect on those organs. Methoxychlor applied to the skin of rabbits caused a dose-related atrophy of the testes, as well as chronic renal disease. Atrophy of the testes and chronic renal disease could not be evaluated in mice and rats because of insufficient data.