During a 24-month period, 350 patients were prospectively studied in an effort to determine the perioperative factors in the development of infections after colon and rectal resections. All patients received standard mechanical bowel preparation; perioperative parenteral cefoxitin (group A) or preoperative oral neomycin and erythromycin, in addition to perioperative cefoxitin (Group B), were also given. Both groups were comparable with respect to age, sex, associated diseases, and primary diagnosis. Wound infections developed in nine of 169 (5%) group B patients and in 15 of 141 (11%) group A patients. Stratification by type of operative procedure revealed that the rectal resections involved the highest rate of infection in group A (22%) and in group B (11%). In patients requiring intraperitoneal colon resection, the rates of wound sepsis were similar (3% in both groups). Analysis of length of operation revealed that in operations lasting 215 minutes or more the infection rate was 12%; in those lasting less than 215 minutes the rate was 4%. Patients with rectal resection and operative times of 215 minutes or more had a wound infection rate of 19% compared to 2% (p less than 0.05) in those with shorter nonrectal operations. Group B patients with the longer rectal operations had lower infection rates (11%) than group A patients (27%), while there was no difference among those who had shorter operations. Intra-abdominal abscesses (p less than 0.01) and anastomotic dehiscence (p less than 0.05) were also significantly reduced in group B patients. Postoperative wound infection is associated with length of operation and location of colon resection and can be significantly lowered by a combination of oral and parenteral antibiotics.