To clarify the nature of null cell acute lymphoblastic leukemia (ALL) we tested null lymphoblasts and other leukemic cells for human T and B lymphocyte antigens detected by reciprocally absorbed rabbit antisera prepared against autologous T and B lymphoblast cell lines HSB-2 and SB. Blasts from 4 of 4 patients with T cell leukemia and from 2 of 10 patients with null cell leukemia expressed T cell but not B cell antigens. Blasts from 8 of 10 patients with null cell leukemia, one patient with B cell leukemia, and 3 of 3 patients with acute myelogenous leukemia expressed B cell but not T cell antigens. T lymphocyte antigen-positive null cell ALL appear to be a form of T cell ALL. B antigen-positive null cell leukemia could arise from either immature B cell precursors or from multipotential stem cells.