The widespread use of coagulation factor concentrates prepared from the blood of numerous donors has doubled the life expectancy of persons with hemophilia, but parenteral exposure to alloantigens and infectious agents is not free of risk. The prevalence of the acquired immunodeficiency syndrome (AIDS) now approaches 1% in patients with hemophilia, and laboratory evidence of abnormal immunoregulation is found in at least 50% of treated patients with severe hemophilia. The immune defect is multifactorial. The attack rate of AIDS among patients with severe hemophilia appears to have reached a peak; further evidence suggests that only a minority of those infected with human T-lymphotropic virus type III will develop AIDS. The advent of improved donor screening methods and the application of heat treatment of coagulation factor concentrates should further reduce the risk of AIDS in persons with hemophilia.