Mycobacterium xenopi infections have rarely been reported among patients infected with the human immunodeficiency virus (HIV), We recently treated two HIV-infected men, neither of whom had a history of pulmonary disease or AIDS-defining conditions, and who had M. xenopi lung infections, Both patients presented with night sweats, cough, and pleuritic chest pain, Chest radiographs showed an upper-lobe nodule in the first patient and a perihilar cavitary infiltrate in the second patient, Both patients were initially believed to have pulmonary tuberculosis and were treated accordingly; however, only M. xenopi grew on cultures of multiple respiratory specimens, This diagnosis was confirmed by cultures of biopsied lung tissue from the first patient and of fluid from a peritracheal abscess in the second patient, Both patients' clinical conditions improved after multidrug therapy (isoniazid, rifampin, pyrazinamide, ethambutol, and ciprofloxacin in the first case; isoniazid, rifampin, and pyrazinamide in the second case), The second patient's condition improved despite in vitro resistance of his isolate to isoniazid and rifampin.