The efficacy and safety of cefotaxime were compared with the efficacy and safety of gentamicin plus clindamycin in the treatment of peritonitis and soft-tissue infection in 112 patients. Patients received 20 mg of intravenous cefotaxime/kg of body weight every 6 hr or 1 mg of gentamicin/kg every 8 hr plus 5 mg of clindamycin/kg every 6 hr (both intravenously). Therapy was continued for five to 10 days. The overall clinical cure rate was 82%, with no significant difference between cure rates in the two groups. Both antibiotic regimens were effective against aerobic and anaerobic isolates, although Pseudomonas aeruginosa, an occasional isolate of Enterobacter, and some anaerobes were resistant to cefotaxime. All clinical failures involved patients who had septicemia or who had received inadequate surgical treatment. Six (11%) of the patients who received combination therapy developed impaired renal function, as indicated by a rise in serum creatinine of 30%. No reduction in renal function was noted in patients given cefotaxime. The clinical efficacy of cefotaxime was equal to that of gentamicin plus clindamycin, and less nephrotoxicity was encountered with cefotaxime.