Human Immunodeficiency Virus (HIV) infection is extremely rare among volunteer blood donors. The highly sensitive Enzyme Linked Immunoassay (ELISA) test and the highly specific Western blot confirmation constitute the test sequence now used to minimize the possibility of transfusion associated HIV infection and to minimize the loss of donors due to false positive test results. The estimated operating characteristics for the test sequence permit the estimation of true infection rates which may be higher or lower than "observed" rates among subcategories of blood donors with progressively lower prevalence rates. The probability that a positive test result indicates true infection also declines with decreasing prevalence. The potential benefits of changing the test sequence so that complete HIV screening is implemented only for donations which are hepatitis-free include a reduction in the costs of Western blot testing and donor counseling, a reduction in the number of donors who use the blood bank inappropriately for personal HIV testing, and a more explicit recognition of the false positive problem when counseling donors.