A 6-year-old girl had fever, abdominal pain, and severe anicteric hepatitis during intravenous oxacillin therapy for staphylococcal osteomyelitis. She had greatly elevated liver enzymes, prolonged prothrombin time, leukopenia, and eosinophilia. Clinical symptoms resolved and laboratory data returned to normal after withdrawing oxacillin and substituting cefazolin. This hepatotoxicity appears to be specific to oxacillin and not to other β-lactams. Monitoring liver function tests during oxacillin therapy, especially in patients receiving prolonged treatment, may be warranted.