A prospective randomized study was undertaken to compare the use of the combination of gentamicin and clindamycin with single agent, cefoxitin, in the treatment of perforated appendicitis in the pediatric patient. In a 3-year period from 1986 to 1989, 56 patients with perforated appendicitis were randomized. Twenty-nine patients received cefoxitin, and 27 patients received gentamicin and clindamycin. Antibiotics were started before operation and continued for a minimum of 6 days after operation. Skin and subcutaneous tissues were left open at surgery and closed secondarily after day 3, if they appeared to be clean. Wounds were considered infected if they developed increased purulence with positive wound cultures. Age range was similar in both groups, with a mean of 9 years (range, 1 to 17 years); 28 were boys and 28 were girls. No changes in antibiotics were required for reasons of susceptibility. No adverse drug reactions occurred in either group. The most common organisms were Escherichia coli in 35 cases (62%) and Bacteroides species in 26 cases (46%). No difference was noted in infection complications in the two groups nor in length of hospital stay. Therefore, no difference is evident in the use of cefoxitin versus gentamicin and clindamycin in the treatment of perforated appendicitis in terms of disease or drug-related complications.