Three cases of ampicillin-resistant Hemophilus influenzae type B septic arthritis are described. These patients presented over a four-month period (November 1978 to February 1979). All were less than 18 months of age, all had positive blood and joint aspirate cultures, and counter-current immunoelectrophoresis (CIE) on serum positive for Hemophilus influenzae type B. The ampicillin minimum inhibitory concentration (MIC) for all three isolates was 6.25 microgram/ml or greater. All patients recovered uneventfully with intravenous chloramphenicol therapy. We suggest that chloramphenicol be considered in the initial therapy of children under 18 months of age who present with septic arthritis, at least in geographic areas where the incidence of ampicillin resistance is high.