Cytomegalovirus (CMV) is the most common recognized cause of viral-induced cogenital malformations, accounting for neurologic injury in more than 5,000 infants each year in the United States alone. We have reported a CMV-specific lymphocyte profliferation defect in infants actively excreting CMV, and suggest that these infants provide a unique model for investigation of mechanisms of immune recognition and immune responsiveness to viral infaction. The immune response to CMV likely represents a complex process involving macrophages, effector T and B lymphocytes bearing specific receptors, and non-effector lymphocytes responsible for the regulation of T and B cell reactivity. Our initial investigations will therefore concentrate on the enumeration of mononuclear cell subsets in infants with active CMV infection and characterization of T and B effector functions in these infants using assays of lymphocyte proliferation, lymphokine production, cytotoxicity, and in vitro antibody synthesis. The specific role of macrophage-T cell interaction in the immune response to CMV will then be studied using purified cell populations from patients and HLA-D related and unrelated control donors. The role of the major histocompatibility complex in genetic restriction and/or regulation of the immune response will then be studied using established fibroblast cell lines from patients and HLA-A and/or B related and unrelated donors in a cytotoxicity assay. Knowledge of cellular immunity to CMV may eventually lead to prevention of primary infection of susceptible individuals and successful treatment of patients clinically affected by the virus.