Objective:To describe the characteristics and outcomes of HIV-infected patients with biopsy-proven cytomegalovirus (CMV) pneumonia.Design:Retrospective study.Setting:A 900-bed acute care facility in New York City.Patients:Eighteen HIV-infected patients with pathologically confirmed CMV inclusions in lung tissue without other pathogens and 36 control patients with biopsy-provenPneumocystis cariniipneumonia (PCP) selected for comparisons by computer-generated random sequential numbers.Main outcome measures:Demographic, clinical, laboratory, radiological findings, and in-hospital mortality.Results:Eighteen HIV-infected patients were found to have CMV lung infection alone. Pathologic findings were pneumonitis (n = 11); pneumonitis and pulmonary vasculitis (n = 1); and CMV inclusions alone (n = 6). All presented with respiratory symptoms (cough or dyspnea), 89% had fever, 83% had radiological abnormalities, and 56% had severe hypoxemia. The pulmonary presentation was similar except for higher lactate dehydrogenase (median, 449 versus 329 IU/l;P= 0.03) and presence of pleural effusions (33 versus 0%;P= 0.001) in CMV patients. Multivariate analysis showed that CD4 counts ≤ 12 × 106/l (odds ratio, 9.2;P= 0.029) and extrapulmonary CMV (odds ratio, 20.4;P= 0.039) were independently associated with CMV pneumonia. Seventeen patients received specific anti-CMV therapy for a mean of 22 ± 13 days. In-hospital mortality was higher in patients with CMV pneumonia (odds ratio, 11.9;P= 0.002). The median time from admission to death was 31 days.Conclusions:CMV lung infection was seen in severely immunosuppressed HIV-positive patients and was associated with clinical pneumonitis with high early mortality. Although the clinical features resemble PCP, the presence of extrapulmonary CMV disease should suggest the diagnosis of CMV pneumonia.