In a prospective study 105 children hospitalized with soft tissue infection, 11 children with suppurative arthritis and 9 children with osteomyelitis were treated with either parenterally administered ampicillin/sulbactam or ceftriaxone. Treatment was randomized using a computer-generated table in a 2:1 fashion: 84 patients received ampicillin/sulbactam and 41 patients received ceftriaxone. Organisms isolated from wound site or blood cultures included Staphylococcus aureus (33), Streptococcus pyogenes (19), Haemophilus influenzae (9) including 4 beta-lactamase-positive organisms, Streptococcus pneumoniae (5), Neisseria gonorrhoeae (3) and 9 other organisms. Clinical and bacteriologic response was satisfactory in 100% of the ampicillin/sulbactam-treated patients and in 93% of the ceftriaxone-treated patients. Two patients with S. aureus infections treated with ceftriaxone had a delayed response and required change in therapy to parenterally administered oxacillin. Ampicillin/sulbactam represents a potentially useful single agent for the treatment of cellulitis and bone or joint infections in pediatric patients.