Ceftriaxone is a new parenteral cephalosporin with a prolonged half-life and an expanded Gram-negative spectrum. Before it can be used as a single agent for infections of unknown etiology, its efficacy in treating infections caused by Gram-positive organisms, particularly Staphylococcus aureus, must be proven. Ceftriaxone was administered to 12 children for treatment of infections due to S. aureus alone or in the presence of other organisms. Sites of infection included soft tissue, respiratory tract, bone and joint. Patients received ceftriaxone at 68 to 100 mg/kg/day in two doses for 3 to 20 days. Clinical and bacteriologic responses were satisfactory in all patients. One patient experienced abdominal pain during infusion and another developed a skin rash. Five patients had platelet counts of 500,000/mm3 or greater; four had an eosinophil count of 7% or greater and one patient had transient neutropenia. These abnormalities resolved during or after therapy. Ceftriaxone was a safe and effective single antibiotic for the treatment of infections caused by S. aureus in children.