Sera from 5,244 blood donations collected between 1979 and 1987 were screened for antibody to HTLV-I with an enzyme immunoassay (EIA) whose result was confirmed with a two-step procedure including Western blot (WB) and radio immunoprecipitation. Of 20 repeatedly reactive samples, two were confirmed positive for HTLV-I infection. These blood units were transfused to patients undergoing cardiac surgery. Both recipients of the confirmed anti-HTLV-I positive units were infected with HTLV-I as evidenced by antibody seroconversion. In contrast, six recipients of EIA positive, WB indeterminate blood and nine recipients WB negative blood were not infected with HTLV-I. These results confirm a low prevalence of HTLV-I infection in US blood donors, the capacity of infected units to transmit the virus to recipients, and the importance of an appropriate confirmatory assay.