The costs and benefits of screening blood donors for antibody to human immunodeficiency virus (HIV) are assessed. Total costs, including testing, discarding processed blood, marginal donor recruiting, notifying and evaluating positive donors, are $36,234,000 annually for 10 million donors in 1986. Screening these donors will prevent 292 cases of transfusion-transmitted acquired immune deficiency syndrome (TT-AIDS), saving the costs of therapy and loss of earnings for total benefits of $43,490,480, a benefit:cost ratio of 1.2:1. Net economic benefits of $0.73 per donor will arise from the program. Calculated benefits will rise as increased numbers of infected recipients are diagnosed with longer follow-up or as partially effective therapy increases the cost of caring for patients with AIDS. Changes in test sensitivity, follow-up procedures, estimated value of life, and testing costs will also alter these projections, but none as dramatically as a change in the overall specificity of the screening process. The cost per case of TT-AIDS prevented, $124,089, and cost per year of life extended, $10,885, are comparable to costs of other screening programs.