Antimicrobial regimens consisting of a brief initial period of parenteral therapy followed by oral therapy were investigated in infants and children with suppurative bone and joint disease. There were 30 patients with acute hematogenous disease (19 osteomyelitis; three osteoarthritis; eight arthritis) and five with subacute or chronic osteomyelitis. Disease was due to Staphylococcus aureus in 26, Hemophilus influenzae in five, streptococci in three, and S. aureus plus Streptococcus pyogenes in one patient. Pus was removed by surgical drainage or needle aspiration. Oral therapy was monitored by assay of antibiotic concentration and bactericidal activity in serum. Adjustments in dosage were made when necessary to assure a peak serum bactericidal titer of at least 1:8. One patient progressed to chronic osteomyelitis but all other patients with acute disease responded well. Oral therapy provides increased patient comfort and decreases the risk of nosocomial infection associated with prolonged intravenous therapy. It should be carried out only under carefully monitored conditions in hospital to assure compliance and adequacy of serum bactericidal activity.