Cytomegaloviurs (CMV) infections are a recognized problem in the first six months after renal transplantation. Studies have suggested that primary infections produce symptomatic disease, whereas reactivation infections are usually asymptomatic. Two patients are described who developed fatal CMV infections in the second year after transplantation. Both patients had typical CMV disease with fever, pneumonitis, and hepatitis. Results of serologic studies in one patient were characteristic of primary infection, with seroconversion at the time of disease and appearance of specific IgM antibodies. The other patient had a similar antibody response at the time of his illness, but serial antibody tests showed that he had had a transient seroconversion earlier, in the second month after transplanation, that was not associated with clinical symptoms. These patients indicate that CMV infection must be considered in the differential diagnosis of serious febrile illnesses even in the late posttransplantation period and may occur either as the result of primary or reactivation infection. Serologic studies at the time of illness may not allow distinction between the types of infection.