The pathogenic importance of cytomegalovirus (CMV) infection in AIDS-associated pneumonitis is controversial. Uncertainty regarding the significance of CMV isolation from pulmonary secretions of AIDS patients results in part from the difficulty in distinguishing CMV infection from CMV disease and from the high frequency of pulmonary CMV co-infection with other opportunistic pathogens. From our review of the literature to date, we have found only three cases in which AIDS patients with hypoxemia and infiltrates on chest x-ray had lung biopsy or autopsy material reported to demonstrate CMV cytopathic effect in the absence of any other pathogen. However, pulmonary CMV co-infection may be a marker of poor outcome in Pneumocystis carinii pneumonia. In this article, appropriate criteria for instituting specific therapy with the antiviral drug ganciclovir are described.