The safety of cefamandole nafate in laboratory animals was evaluated in six species. The acute toxicity of cefamandole after intravenous or subcutaneous administration was similar to that of cephalothin sodium. The subacute and chronic toxicity of cefamandole was studied in rats and dogs for periods of two weeks to six months at doses of 250--1,000 mg/kg per day in rats and 125--1,500 mg/kg per day in dogs. No evidence of significant systemic toxicity was observed in these studies. There were, however, various degrees of local injury at the injection sites that resulted in slight decreases in hemoglobin, hematocrit, and red blood cell counts in the animals in which injury at the injection site was most severe. Studies of reproduction in rats and mice indicated that cefamandole nafate had no teratogenic effects and no adverse effects on fertility, gestation, or growth of offspring. Comparative studies of nephrotoxicity in rabbits demonstrated that the nephrotoxicity of cefamandole nafate was considerably less than that of cefazolin.