The expression of HLA class I- like molecules was analyzed on human acute and chronic leukemic cells. The presence on leukemic cells of class I- like molecules, absent on the patient's normal lymphocytes, was examined by complement- dependent lymphocytotoxicity using platelet absorbed alloantisera that recognize HLA-linked, 45-12 kd, beta-2-microglobulin associated molecules, selectively expressed on PHA-activated cells. A positive reactivity of the anti- class I- like alloantisera was found in 50% of the acute leukemias (cALL, T-ALL and AML), independently of the lineage of differentiation, while chronic lymphocytic leukemias (B-CLL) were constantly negative. It is suggested that beta-2-microglobulin associated HLA molecules may represent markers of leukemic blast activation and/or maturation state.