The occurrence of life-threatening infections, including cytomegalovirus (CMV) infection, in recipients of allogeneic bone marrow transplants is related to the severe and prolonged immunodeficiency that is present after transplantation. Studies performed in our laboratory of the recovery of CMV-specific T cell responses after bone marrow transplantation have demonstrated that CMV disease occurs exclusively in those patients with no reconstitution of CD8+ CMV-specific T cell responses. Methods of isolating class I major histocompatibility complex-restricted CD8+ CMV-specific T cell clones from healthy CMV-seropositive individuals with protective immunity have been developed. The majority of cytotoxic T cell clones isolated from several individuals recognize structural proteins of the virion that are presented by infected cells without requiring the expression of the viral gene. These results suggest this immunodominant response may be essential for maintaining the virus in a latent state in healthy CMV-seropositive individuals. Clinical trials have been initiated at our institution to investigate the potential for selective reconstitution of CMV-specific immunity in bone marrow transplant recipients by the adoptive transfer of CMV-specific T cell clones generated from the respective bone marrow donor.