Antibiotic prophylaxis for surgery has appeared indicated whenever likelihood of infection is great or consequences of such are catastrophic. For better clarification, a prospective, randomized, double-blind study was run on 400 patients undergoing elective gastric, biliary, and colonic operations. There were four treatment categories, with antibiotic being instituted 12 hours preoperatively, just prior to operation, after operation, or not at all. During operation, samples of blood, viscera, muscle, and fat were taken for determination of antibiotic concentration. Both aerobic and anareobic cultures were also taken of any viscus entered, peritoneal cavity, and incision. Similar cultures were run on all postoperative infections. Results demonstrated that the incidence of wound infection could be reduced significantly by the preoperative administration of antibiotic in operations on the stomach (22% to 4%), on the biliary tract (11% to 2%), and large bowel (16% to 6%). Less impressive results were obtained for peritoneal sepsis. Initiation of antibiotic postoperatively gave an almost identical infection rate as if antibiotic had not been given (15% and 16%, respectively).