Eight human sera from healthy individuals with no history of immunization with human transplantation antigens have demonstrated complement dependent cytotoxicity to cells of some patients with active acute leukemia. The antigen(s) detected by these sera are absent from normal and remission lymphocytes and appear most often in ALL patients with a high peripheral lymphoblast count. Some B and T lymphoblastoid cell lines carry the antigen(s) as evidenced by their ability to react with and absorb the antileukemia activity. The data support the existence of at least two overlapping specificities detected by these antileukemia sera. The leukemia antigen(s) show no strong correlation with any known HLA antigen. These observations provide evidence for a human leukemia blast associated antigen or set of antigens which may be immunogenic in man. Their relationship to normal HLA antigens of loci other than A, B or C is unknown.