This study assessed the incidence and clinical significance of recovery of Staphylococcus aureus from the respiratory tract of patients infected with the human immunodeficiency virus (HIV). In a retrospective review of 129 consecutive episodes of respiratory disease in HIV-seropositive patients where respiratory tract cultures were obtained, S. aureus was recovered in 30 (23%) of the episodes. Twenty-nine of these were evaluated in this study, and the recovery of S. aureus was found to represent pneumonia in 8 cases (28%), to be of indeterminate significance in 18 cases (62%), and to represent colonization in 3 cases (10%). Episodes of S. aureus pneumonia were usually community-acquired (seven of eight episodes) and had an acute or subacute clinical presentation. Fever and physical signs of pneumonia were present in all patients. Chest radiographic presentations varied, but local infiltrates were seen in seven of eight episodes. Concomitant pulmonary disorders were common (seven of eight episodes). All patients were appropriately treated; five patients recovered and three died, giving a mortality rate of 38%. We conclude that S. aureus is a frequent isolate from respiratory tract cultures of HIV-seropositive patients referred for evaluation of pulmonary disease. It can cause a pneumonia with a high mortality rate, as it did in 6% of all episodes of pulmonary disease reviewed in this study. Clinicians should be aware that HIV-seropositive patients may develop respiratory disease secondary to S. aureus infection and that when this organism is suspected, appropriate antibiotic therapy should be instituted.