Previous reports of infection due to Mycobacterium kansasii among patients infected with human immunodeficiency virus (HIV) have conflicted with regard to the significance of the isolate; the clinical, radiographic, and laboratory features of the disease; and the response to therapy. To clarify the spectrum of M. kansasii infection in this population, we conducted a retrospective study of 35 patients. Twenty-eight of these patients were believed to have disease due to M. kansasii, while the remaining seven patients were probably colonized with the organism. All but two patients presented with advanced HIV infection; the median CD4 cell count was 12/microL. Most patients with pulmonary disease presented with fever, cough, and dyspnea, but only eight of these 22 patients had radiographic findings of either pulmonary cavitation or predominantly upper-lobe disease. Ten patients had M. kansasii isolated from blood or bone marrow. The majority of patients with pulmonary or disseminated disease responded to therapy. However, 11 patients died either before mycobacterial infection was diagnosed or early in the course of treatment, and two had a relapse of infection during therapy.