Human cytomegalovirus (HCMV) is a prevalent herpes virus that produces lifelong persistent, but asymptomatic, infections in healthy humans. However, it causes substantial morbidity and mortality in immunocompromised patients, including AIDS patients and immunosuppressed solid organ/bone marrow transplant recipients. HCMV is also a leading cause of birth defects following congenital infection of fetuses. Research is needed to understand mechanisms of viral persistence, approaches to preventing fetal infection in pregnant women, and development of anti-herpesvirus chemotherapies. The Barry Laboratory is utilizing rhesus cytomegalovirus (RhCMV) in its natural host, the rhesus macaque, as a model of human infection. RhCMV closely mimics the human virus, including persistent infection, activation in immunocompromised hosts, and congenital infection of the fetus, in which infants exhibit outcomes similar to human infants congenitally infected with HCMV. These studies help to understand the kinetics and specificity of the host immune response to form the foundation for pathogenesis, chemotherapy, and vaccine studies. Development of anti-viral chemotherapy approaches involves collaboration with the North Laboratory.