Cytomegalovirus (CMV) pneumonitis is an important cause of morbidity and mortality in lung transplant patients and requires timely and accurate diagnosis. This study compares the diagnostic utility of the evaluation of transbronchial biopsy by histology, immunohistochemistry, and simultaneous culture of bronchoalveolar lavage in a population of 13 lung transplant patients who underwent 78 biopsies during a period of 27 months. Our study concludes that, in patients clinically symptomatic for CMV pneumonitis, histology alone is diagnostic for the presence of the virus, whereas culture of bronchoalveolar lavage fluid is not as helpful. In asymptomatic patients, however, immunohistochemistry utilizing monoclonal antibodies to immediate-early and early CMV nuclear antigens may indicate development of CMV pneumonitis before cytopathic changes are evident.