The incidence of infections among patients undergoing renal transplantation has been reported as high as 83% during the first post-transplant year. In an effort to reduce the occurrence of such infections, we evaluated the role of perioperative prophylactic antibiotics in these patients. Thirty-seven patients undergoing transplantation were assigned randomly to treatment groups (N=20, cefamandole, 1 gm IM every 6 hrs for 8 doses/tobramycin 1 mg/kg IM for 1 dose, starting 2 hrs prior to surgery) and control groups (N=17, no antibiotics). A uniform infection surveillance system was used. Eighty-one percent (30/37) of patients became infected; 70% (14/20) of treated patients and 94% (16/17) of controls (p=0.14). Since antibiotic prophylaxis might be expected to exert the greatest influence in the immediate postoperative period, we examined patient outcome data for both the first seven post-transplant days and for the entire hospitalization. Of the 38% (14/37) of patients who developed infections during the first posttransplant week, a statistically greater proportion came from the control group than from the treated group (10/17 vs. 4/20, p=0.04). These data suggest that this regimen is effective in reducing the occurrence of infections during the first week following renal transplantation.