The prevalence of total as well as IgM antibodies against cytomegalovirus (CMV) was determined by enzyme immunoassay in a group of 287 multitransfused thalassemia major patients aged 5–39 years and in another group of 1,220 healthy controls. A significantly higher prevalence of CMV antibodies was observed in thalassemic patients of all age-groups compared with controls. The prevalence among splenectomized thalassemic patients was higher than among nonsplenectomized thalassemics. It is concluded that patients with thalassemia, especially if splenectomized, are at high risk for transfusion-transmitted CMV infections. The high prevalence of CMV infections might be responsible, at least in part, for the immunological disturbances and the susceptibility to other infections observed in thalassemic patients. On the basis of these results, it is suggested that safe blood should be provided for anti-CMV-negative thalassemics, with priority to anti-HIV-positives and those who are to receive bone marrow transplantation.