In a prospective randomised trial in which 93 patients undergoing elective colorectal operations were given a short prophylactic course of metronidazole and kanamycin orally or systemically, postoperative sepsis occurred in only 3 (6.5%) of those given antimicrobials systemically, compared with 17 (36%) of those given oral prophylaxis (P less than 0.01). 15 of the 17 infections in patients who received antimicrobials orally were due to kanamycin-resistant bacteria present in the colon at operation. Bacterial overgrowth of Staphylococcus aureus was recorded in 6 of the patients who received oral therapy. Antibiotic-associated pseudomembranous colitis occurred in 7 patients, 6 of whom had received prophylaxis orally. These results indicate that oral administration of prophylactic antimicrobials in colon surgery should be avoided because of the risks of bacterial resistance, superinfection, and antibiotic-associated pseudomembranous colitis. Systemic per-operative antimicrobial prophylaxis is safer and more effective.