In a prospective study of 107 patients undergoing surgery for gastroduodenal disease, antibiotics were withheld from a group of 24 patients defined preoperatively to be at low risk of developing postoperative infections; no wound infection occurred in this group. Perioperative cephaloridine was randomized among the remaining patients (high risk). Wound infections developed in 11 of 42 patients who did not receive cephaloridine, but in none of the 41 patients who were given cephaloridine (p less than 0.02). Coliform bacteria were grown only from swabs of the stomach mucosa of patients in the high risk group and were the main cause of wound infections. Severe preoperative lymphocytopenia was frequently associated with the development of serious postoperative sepsis. The results validate a policy of restricting antibiotic prophylaxis in gastroduodenal operations to patients at high risk of postoperative infection and suggest a new risk factor--the preoperative blood lymphocyte count.