The clinical and diagnostic features of 29 adult patients with H. influenzae septic arthritis are reviewed. Twelve men and 17 women ranging in age from 22 to 82 years developed the infection. H. influenzae septic arthritis is an acute, febrile disease with a mean duration of symptoms before diagnosis of 4 days. Fifteen patients had monoarticular arthritis, 6 with an infected knee. Polyarticular involvement, with a range of 2 to 9 joints, was diagnosed in 14 patients. Nineteen patients had concurrent extraarticular sites of infection, including meningitis, pneumonia, pharyngitis, sinusitis, conjunctivitis, and cellulitis. Twenty-two of 29 patients had predisposing factors for infection, including ethanolism, trauma, rheumatoid arthritis, systemic lupus erythematosus, diabetes mellitus, splenectomy, multiple myeloma, lymphoma, gout, and acquired common variable hypogammaglobulinemia. Characteristic synovial fluid findings included purulent, greenish fluid, elevated WBC count, and gram-negative pleomorphic microorganisms. Treatment for these patients included antibiotic therapy, most often ampicillin and chloramphenicol, and joint drainage by repeated arthrocentesis or arthrotomy. A favorable outcome was reported in 25 of 29 patients. Hemophilus influenzae septic arthritis should be suspected in adults who are immunocompromised and have a concurrent extraarticular source of infection.