The risk of inpatient-to-nurse transmission of cytomegalovirus (CMV) was assessed in a five-year prospective seroepidemiologic study. We enrolled 263 renal transplant/hemodialysis nurses, 204 neonatal intensive care nurses, 225 student nurses, and 251 blood donor controls. Prevalence of CMV antibody in these 943 subjects was 33.7% and did not differ significantly among the four study groups. Sixteen subjects experienced primary CMV infections. The yearly seroconversion rate, calculated from age-related seroprevalence data, was 1.9%. The rate of seroconversion during the study, established by observing 519 seronegative subjects for 10 420 person-months, was 1.84% per year and did not differ significantly among the study groups. The proportions of patients with CMV infection (1.1% to 11.9%) and disease (0.5% to 3.4%) on study wards were not related to seroconversion in the nurses. The slow rate of acquisition of CMV in susceptible adults suggests that transmission requires prolonged, intimate contact. Nurses and nursing students who practice good personal hygiene are no more likely to acquire CMV than their peers in the community.