Despite recent enthusiasm for antibiotic prophylaxis by uterine irrigation at the time of cesarean section, no data exists comparing the efficacy of this technique with standard intravenous antibiotic administration. Therefore, 124 patients about to undergo cesarean section were entered into a prospective, randomized, double-blind evaluation of uterine irrigation versus intravenous administration of either normal saline or cefoxitin. All women were considered to be at increased risk for postoperative infection because of the presence of labor or ruptured membranes. The incidence of endometritis and the fever index in patients receiving intravenous cefoxitin (3.2%, 4.6 degree hours) was significantly less than in patients receiving intravenous normal saline (21.2%, 22.3 degree hours). There was no significant difference between the use of intravenous normal saline and uterine irrigation with either cefoxitin (18.9%, 16.6 degree hours) or normal saline (17.4%, 24.6 degree hours). These results suggest that intravenous infusion is the most effective means of administering cefoxitin as a prophylactic antibiotic.