A prospective and randomized clinical study was conducted in order to compare cefoxitin (CFX) and ceftizoxime (CZX) as prophylactic antibiotics. Two hundred and three consecutive cases of elective upper gastrointestinal tract surgery, performed at our institute between January, 1983, and March, 1986, were entered in the trial. The patients were assigned randomly, before surgery, to the CFX or to the CZX group. Two grams of the assigned antibiotic was first administered during surgery and then continued at a dose of 1 gram, every 8 hrs for a total of 4 days. One patient was withdrawn from the study due to an allergic reaction. Both groups were comparable in sex, age, underlying disease, diagnosis, operation, and preoperative laboratory data. There were 18 infections related to the operation in the CFX group, while there were only 3 in the CZX group (p less than 0.001). The number of unrelated infections in each group was 6 and 6 respectively (NS). No special differences were found between the two groups regarding the kinds of microorganisms isolated, and no significant differences were seen in the adverse effects of either antibiotic. Our study demonstrated that ceftizoxime was more efficient than cefoxitin in preventing postoperative infection, following upper gastrointestinal tract surgery.