The toxicity profile of silodosin, a selective alpha(1A)-adrenoceptor antagonist, was evaluated. The lethal doses were 800 mg/kg in rats and 1500 mg/kg in dogs. Repeated-dose studies revealed fatty degeneration of hepatocytes and an induction of drug-metabolizing enzymes at 15 mg/kg/day or more in male rats, mammary gland hyperplasia at 60 mg/kg/day or more in female rats, and degeneration of the seminiferous tubular epithelium at 25 mg/kg/day or more only in young dogs. Silodosin was negative in all mutagenicity studies, except for a weak positive in a chromosomal aberration assay conducted without metabolic activation. In carcinogenicity studies, mammary gland tumors and pituitary adenomas were increased in female mice given 150 mg/kg/day or more and 400 mg/kg/day respectively, while thyroid follicular cell carcinoma was increased in male rats given 150 mg/kg/day. Reproductive studies in rats revealed a decreased male fertility at 20 mg/kg/day or more and a prolonged estrous cycle at 60 mg/kg/day or more. Silodosin did not exhibit any teratogenic potential in either rats or rabbits, and had no effects on the postnatal development of rat offspring. In safety pharmacology studies, silodosin produced no severe effects on the central nervous, cardiovascular, or respiratory systems. In conclusion, silodosin exhibited adequate safety margins between the clinically recommended dose and those at which toxic effects or safety pharmacological changes were detected. As a new therapeutic drug for the micturition difficulties caused by benign prostatic hyperplasia, silodosin should have few serious side effects in clinical use.