The administration of cephradine prophylactically to patients who were undergoing vaginal hysterectomies resulted in a marked and significant reduction in the incidence of postoperative infections when compared to a placebo group. Cephradine was the cephalosporin studied because of its unique pharmacodynamic properties, which result in high uterine tissue levels. The protective effect was similar whether I g was given preoperatively followed by 500 mg IV q. 6 hours for 4 doses, or a single dose of 2 g IV given approximately 1 hour before surgery. Uterine tissue and serum levels of antibiotic were high and correlated with the degree of protection noted.