In an open, randomized, comparative study, patients with bone, joint, or soft-tissue infections were treated with sulbactam sodium plus ampicillin (sulbactam/ampicillin, 1 g of sulbactam and 2 g of ampicillin three times a day) or with cefotaxime (2 g three times a day) for two weeks as initial therapy. Thirteen patients were entered into the sulbactam/ ampicillin group and nine into the cefotaxime group. Two weeks after the end of therapy, clinical cure or improvement was observed in all 13 patients treated with sulbactam/ampicillin and in sevenof nine patients treated with cefotaxime. Staphylococcus aureus was not eliminated from one patient in each group. Recurrence of S. aureus infection occurred in two patients in the cefotaxime group within two weeks after the end of therapy. No adverse effects warranting discontinuation of antibiotic therapy were observed. The combination of sulbactam sodium plus ampicillin was at least equivalent to cefotaxime for the initial treatment of acute serious soft tissue and bone and joint infections.