In this prospective, comparative study, 129 patients who sustained penetrating abdominal trauma were randomized to receive preoperatively, and for 3-5 days postoperatively, one of three antibiotic regimens: Group I--cefotaxime (CTX) (2 Gm Q8H), Group II--cefoxitin (2 Gm Q6H), or Group III--clindamycin (900 mg Q8H) and gentamicin (3-5 mg/kg/day in divided doses Q8H). The three groups were similar in terms of the following: age, sex, severity of injury, number of organs injured, colon injuries, shock, blood transfusions, or positive intraoperative cultures. Septic complications occurred as follows: Group I--6.9%, Group II--2.3%, and Group III--6.9%. The three regimens ranked as follows in terms of therapy costs: CTX less than cefoxitin less than clindamycin and gentamicin. It is concluded that single agent therapy with a cephalosporin is preferable to combination therapy on the basis of equivalent effectiveness, lower toxicity, and lower costs.