A panel of sera with leukoagglutinin activity was obtained from patients who had received multiple blood transfusions. Leukocytes of identical twins presented identical reaction patterns when tested against these sera, although no two unrelated subjects had identical leukocytes. None of the sera had identical reaction patterns with a panel of leukocytes from different subjects. Family studies failed to identify specific leukocyte antigens. It is concluded that there is a multiplicity of leukocyte antigens and that these are not related to erythrocyte antigens. The data suggest that febrile transfusion reactions in patients with leukoagglutinins may be avoided by use of bloods with compatible leukocytes.