We conducted a retrospective review of 21 adult patients with osteomyelitis and septic arthritis who were treated with high doses of oral antimicrobial agents, usually after an initial course of intravenous therapy. The mean duration of parenteral and oral therapy was 3.6 days and 43.0 days, respectively. Absorption of oral antibiotics was assessed by determining the trough serum bactericidal titers for the infecting organism; whenever feasible, the dosages were adjusted to achieve trough titers greater than or equal to 1:8. The follow-up period ranged from six to 66 months (mean, 42.4 months). Eighteen of 21 patients had no clinical signs of recurrence after initial therapy. One patient with an infected joint prosthesis developed recurrent infection, and two patients had recurrences accompanied by sequestra. The mean duration of hospitalization was 13.4 days, and the mean duration of outpatient treatment was 31.9 days.