Shortly after the first cases of AIDS were reported in 1981, it became apparent that this disease was caused by a blood-borne infectious agent that could be transmitted by blood transfusion. Early reports documented a reduced ratio of CD4+ to CD8+ T cells not only in AIDS patients but also in likely carriers of the AIDS pathogen. On this basis, from July 1983 to June 1985, our blood center utilized flow cytometry to test each donated unit for the ratio of CD4 to CD8 T cells; we did not transfuse blood from donors with CD4/CD8 < 0.85. Despite available data supporting the utility of this or other surrogate blood tests to screen blood donors, the vast majority of blood banks did not initiate blood donor testing for AIDS until 1985, following the discovery of HIV and development of commercial HIV antibody tests. Retrospective analysis indicates that donor screening with surrogate markers would have removed the majority of AIDS-contaminated units from the blood supply and prevented a substantial fraction of the estimated 10,000 cases of transfusion-transmitted AIDS in the United States. In this report, we review the events that led to our decision to initiate blood donor testing prior to the identification of HIV, the results of such testing, the consequences of the decision by most blood banks not to initiate such testing, the current status of the blood supply with respect to HIV, and steps that can be taken in the future to protect the blood supply from new pathogens.