Herpesviruses characteristically establish latent infections in their hosts. In some instances, the tissue sites or even the specific cells that harbor dormant virus have been identified experimentally. However, the sites of cytomegalovirus (CMV) latency have been difficult to define experimentally in humans, even though epidemiologic evidence indicates that undetectable virus can be transferred from donor to recipient in transfused blood or a transplanted organ. Recently, DNA of human CMV has been found in peripheral blood leukocytes and in normal or malignant colonic tissue by hybridization methods. Studies in mice strongly implicate splenic B lymphocytes as cellular reservoirs of latent CMV; however, the virus may also persist in the salivary glands, the prostate, the testes, peripheral blood, and possibly macrophages. Whether latent CMV infection in these tissues is maintained in a single ubiquitous cell type (e.g., lymphocytes or macrophages) or in various cell types is not known. Definition of the sites and mechanisms involved in the maintenance of latent CMV is essential for a thorough understanding of the pathogenesis of CMV infection. Now that trials with live CMV vaccine have begun, further investigations of latent CMV infection in humans and in animal models are clearly needed.