Seventy hospitalized women were entered into an open, randomized, parallel study of antimicrobial prophylaxis for abdominal and vaginal hysterectomy with the use of either cefotetan, a new long-acting cephalosporin, or cefoxitin. Ninety-four percent of cefotetan recipients and 83% of cefoxitin recipients did not develop clinical signs or symptoms of infection. The satisfactory bacteriologic response rates were significantly different: 91% satisfactory (43 of 47 patients) for cefotetan and 74% satisfactory (17 of 23 patients) for cefoxitin. The two treatment groups demonstrated no significant differences in postoperative temperature changes, duration of hospitalization, or grading of surgical wounds. Neither drug was associated with significant side effects.