We evaluated three 1-g doses of cefmetazole in comparison with the standard three 2-g doses of cefoxitin for prophylaxis in vaginal or abdominal hysterectomy to determine efficacy and safety. The antibiotics were administered intravenously 30-90 min before the incision and were followed with additional intravenous doses 8 and 16 h or 6 and 12 h later, respectively. The patients received povidone-iodine vaginal preparations before surgery; vaginal packs, when used, contained no antibiotic agents. Vaginal cultures were obtained before the vaginal preparation, at the time of discharge from hospital and when there was a suggestion of operative site infection. The activity of both antibiotics against these organisms was tested. Patient demographic characteristics and surgical procedures were similar in each treatment group. The difference between the primary failure rates with the two antibiotics (2 of 35 (5.7%) with cefmetazole and 2 of 16 (12.5%) with cefoxitin) did not reach statistical significance, and results were similar for the two routes of hysterectomy. Cefmetazole was more active than cefoxitin against the majority of the aerobic and anaerobic organisms recovered, although approximately 20-30% of the isolates showed resistance, or intermediate sensitivity, generally to both antibiotics.