The toxicity of rioprostil was extensively investigated. Studies in rodents, dogs and monkeys indicate a low order of acute toxicity. Oral subchronic and chronic toxicity studies in rats and dogs produce effects that would be expected based on the pharmacological activity of the compound. In reproduction studies with rioprostil, male and female fertility is unaffected in rats at doses up to 2.0 mg/kg/day and there is no evidence of embryotoxicity, fetotoxicity, or teratogenicity in rats at doses up to 1.7 mg/kg/day. In rabbits a maternally toxic dose (1.5 mg/kg) also increases resorptions, reduces fetal weight, and increases the incidence of malformations. Evaluation of 24-month carcinogenicity studies in mice and rats at oral doses up to 2.0 and 1.5 mg/kg/day, respectively, are in progress. Mutagenicity studies are negative.