An antigen with a molecular weight of 150 kilodaltons expressed on certain leukemia and lymphoma cells was recognized by a human monoclonal antibody (3H12), which had been established by the fusion of lymphocytes from a small cell lung cancer patient with a mouse myeloma cell line (P3U1). Peripheral blood mononuclear cells from 3 out of 4 cases with lymphoid crisis of chronic myelogenous leukemia (CML) were positively stained by 3H12, while cells from 5 cases with myeloid crisis of CML did not react to this antibody. The antibody did not show any reactivity to cells from the chronic phase of CML, other types of leukemias or normal hematopoietic cells. We further examined 29 cell lines of hematopoietic origin and found that 2 undifferentiated cells (BV-173 and K-562) reacted to the 3H12 antibody. In addition, we found that 3 out of 6 Burkitt lymphoma cells (DAUDI, RAJI and HR1K) reacted to 3H12. Taken together, these results suggest that the antigen recognized by 3H12 is a differentiation-associated antigen expressed on immature lymphoid cells, and could potentially be a reliable cell lineage marker.