To determine the efficacy of enzyme immunoassays (EIAs) for antibodies against HIV-1 in detecting HIV-2-infected blood, we tested 55 HIV-2-positive sera with seven Food and Drug Administration-licensed EIA kits. The percentage detection of HIV-2 sera giving positive reactions with these kits varied between the various manufacturers from 60 to 91%. Observations based on a small number of sera (n = 13), suggest that HIV-2-positive blood collected from apparently healthy people (blood donors, prenatal clinics) are detected with a greater frequency (means = 89%) than blood from AIDS patients or patients (n = 32) hospitalized with other infectious diseases (means = 72%). Based on these results and the low incidence of HIV-2 infection observed in the USA, it was concluded that screening with HIV-2-specific tests would not significantly increase the number of HIV-2-positive people detected by current screening programs. However, due to the poor sensitivity of certain HIV-1 assays for HIV-2 antibodies, HIV-2 sera without cross-reacting antibodies will escape detection. Surveillance for HIV-2 might then be improved by the availability of HIV-1 and HIV-2 combination assays.