The efficacy of cefoxitin, either alone or in combination (+/-) with an aminoglycoside was compared with clindamycin plus (+), an aminoglycoside for the treatment of mixed aerobic-anaerobic surgical infections, in a prospective randomized single blinded study. One hundred patients were entered into the study; 37 patients were assessable for clinical outcome in both groups, while toxicity could be assessed in 46 patients in the cefoxitin group and 47 in the clindamycin group. The groups were evenly matched considering age, sex, and type of infection. Favorable clinical responses were achieved in 34 of 37 patients treated with cefoxitin +/- amikacin, and 29 of 37 patients treated with clindamycin + amikacin; there was no statistical difference between the groups (p greater than 0.1). The incidences of toxicity were the same. Our study has demonstrated that cefoxitin with or without an aminoglycoside is as effective as clindamycin plus an aminoglycoside in the therapy of serious mixed infections in surgical patients.