Toxicity, antifertility, and endocrine effects of gossypol have been studied in male rats. The animals grew nearly normally when administered a daily dose of 7.5 mg/kg orally for 12 wk. At 15 and 30 mg/kg/d doses growth rates were significantly reduced. Infertility occurred at all dose levels, but mating behavior was maintained throughout the period of treatment. Examination of the cauda epididymis after 6 wk at the 30-mg/kg/d dose and after 12 wk at the lower doses showed reductions in sperm numbers as compared with controls. All of the sperm from the groups receiving the 15- and 30-mg/kg/d doses were immotile; and at the 7.5-mg/kg/d dose level most sperm were immotile. Many of nonmotile sperm showed sharply bent tails or lacked tails. There was no significant change in the serum levels of testosterone, LH, or FSH in animals receiving 7.5 and 15 mg/kg/d of gossypol for 12 wk. However, at a dose of 30 mg/kg/d for 6 wk, the serum testosterone and LH concentrations were significantly reduced. FSH concentrations remained normal in all groups. A group of 5 animals receiving 15 mg/kg/d were allowed a recovery period of 6 wk after 12 wk of therapy and they evidenced complete recovery of fertility.