Oral and intravenous (IV) antibiotic regimens were compared in 15 children with etiologically defined osteomyelitis and/or septic arthritis. On admission all children were started on standard IV therapy; seven were changed to oral antibiotics within 72 hours and the remaining eight continued on IV therapy for four weeks. Oral antibiotic doses were adjusted to achieve a peak serum bactericidal titer of greater than or equal to 1:8 against the patient's own pathogen. All patients were treated in hospital for four weeks; therapy continued for a minimum of six weeks or until the erythrocyte sedimentation rate (ESR) fell below 20 mm/hr. The clinical course and outcome were similar in both groups. There were no treatment failures nor any relapses during a 12-month follow-up period. This prospective study supports, with controlled data, the concept that acute skeletal infections can be safely and successfully treated with carefully monitored oral therapy.