In 1985, serologic testing became available to screen blood donors for the viruses associated with the acquired immunodeficiency syndrome; these viruses are now called human immunodeficiency viruses I and II. In 1989, blood donor screening for other retroviruses, human T-cell lymphotropic viruses I and II, was initiated. This article describes the evolution of testing protocols for blood donors for these viruses, disease manifestations associated with seropositivity, the efficacy of donor screening including testing for these retroviruses, and counseling recommendations for positive blood donors with confirmed infection.