In a controlled, randomized study the effect of penicillin and streptomycin on postoperative septic complications in colorectal surgery (penicillin, 2 ml, IU, intramuscularly, three times daily for a period of six days and concomitantly streptomycin, 0.5 gm, intramuscularly, two times daily for a period of four days) was compared with the effect of cefotaxime, 2 gm, intravenously, three times on the day of surgery. One hundred patients completed the study: 48 were treated with penicillin and streptomycin (Group 1) and 52 with cefotaxime (Group 2). Wound infection occurred in one patient (2.1 percent) in Group 1, but not in Group 2 (0%, N.S.). Rupture of the wound occurred in one patient in each group (2.1 percent vs. 1.9 percent, N.S.). Insufficiency of the anastomosis occurred in four patients in Group 1 (8.3 percent) and in one patient in Group 2 (1.9 percent). It is concluded that short-term prophylaxis with cefotaxime is as effective as long-term prophylaxis with penicillin and streptomycin.