We examined the effects of the immunosuppressive drug cyclosporine A on male reproduction in sexually mature rats. The drug was administered subcutaneously in 3 doses (10, 20 and 40 mg. per kg. daily) for 14 days. Cyclosporine A administration resulted in a dose-dependent decline in body and reproductive organ weights, histology of the testis showed definite degenerative changes, and sperm counts and motility decreased. Spermatozoa from treated rats retained the cytoplasmic droplet and they were decapitated. Consequently, sterility occurred in rats treated with high doses of cyclosporine A. A reduction in circulating testosterone and an increase in gonadotropins were noted. The possibility existed that the cyclosporine A-induced alterations in the male reproductive system were secondary to the hepatic or nephrotoxic effects of the drug. Therefore, we assessed liver and kidney function by assay of the serum levels of bilirubin, alkaline phosphatase, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase and creatinine. Except for an increase in bilirubin, none of the other liver function studies was altered, thereby eliminating hepatocellular damage as the etiology of impaired reproductive function in cyclosporine A-treated rats. We observed an increase in creatinine levels in animals treated with higher doses of cyclosporine A, consistent with mild renal failure. However, the fact that a decline in reproductive function was seen even in the group treated with 10 mg. per kg. cyclosporine A daily, which had normal serum creatinine levels, suggests that the alterations in male reproduction seen with this therapy are not entirely the result of nephrotoxicity.