A randomized prospective study of antibiotic prophylaxis was carried out in patients who underwent elective surgery of the colon. The wound infection rate in 70 patients who received cephradine intravenously in the perioperative period (group 1) was 25%, compared with 8% in 60 patients who received metronidazole and erythromycin base orally before operation (group 2). Both Bacteroides fragilis and Escherichia coli were cultured from the majority of wound infections in group 1, but B. fragilis was not found in any group 2 patients. Wound contamination indicated by wound class or by culture of the subcutaneous tissue of the wound before closure was the best predictor of subsequent wound infections. These results suggest a dominant role for intestinal anaerobes in the genesis of wound infections after colonic surgery and show that antibiotics specifically directed against these organisms can substantially reduce the rate of wound infection.