1. A previously untransfused dialysis patient was given blood from a single donor on three occasions and sera were obtained from the recipient before and after transfusion. 2. The sera were tested against B-lymphocytes from the blood donor and his family in the erythrocyte–antibody rosette inhibition assay to determine whether any Fc-receptor-blocking activity which developed was HLA linked. 3. Antibody activity was noted after the second transfusion and was directed toward B-lymphocytes from the blood donor and his family members sharing the haplotype HLA A11, B12 with him. 4. These antibodies were removed by the absorption of active sera with lymphocytes from the blood donor but not from (a) his sibling who shared no HLA antigens with him or (b) the transfusion recipient. Absorption of the active sera with platelets from the blood donor did not remove activity. 5. These results indicate that Fc-receptor-blocking antibodies developing after blood transfusion are directed to HLA-linked antigens on donor lymphocytes.