We report treatment decisions and outcomes for 20 patients who were infected with human immunodeficiency virus type 1 (HIV-1) and were receiving highly active antiretroviral therapy (HAART) who had respiratory symptoms and from whom Mycobacterium xenopi was isolated. All patients also had coexisting pulmonary pathologic conditions. The median blood T cell CD4 count was 37 cells/μL (range, 2-480 cells/μL). Fifteen of 20 patients received no antimycobacterial therapy and remain healthy after a median of ∼4 years of follow-up, and 2 patients required treatment specifically for M. xenopi infection, both showing clinical improvement. We conclude that pulmonary M. xenopi isolation in HIV-1 patients receiving HAART does not usually require specific treatment.