The emergence and spread of ampicillin-resistant Haemophilus influenzae type b strains have led to a sharp reduction in the use of ampicillin, or the addition of chloramphenicol, in the initial therapy of serious childhood infections. In some instances, third generation cephalosporins are used instead. The combination of ampicillin with sulbactam restores the former usefulness of ampicillin and extends its spectrum of activity to include normally ampicillin-resistant Staphylococcus aureus. Sulbactam/ampicillin should be useful in treating bacterial meningitis. It is more effective than third generation cephalosporins against Listeria and enterococci, and is more effective than ampicillin against Enterobacteriaceae. The combination also holds promise as a treatment for soft tissue, bone and joint infections in children.