Appropriately absorbed antisera to the lymphoblastoid cell lines HSB and SB detect a human T-lymphocyte-associated antigen (TLAA) and the human Ia-like antigens, respectively. Cells from some patients with acute myelomonocytic leukemia (AMML) and chronic myelogenous leukemia in blast crisis expressed both TLAA and Ia antigens when tested in a complement-dependent microcytotoxicity assay (greater than 90% lysis with both antisera). When patients were in remission, expression of TLAA and Ia antigens returned to normal values. Quantitative absorption of anti-TLAA serum with increasing numbers of AMML cells showed that these cells could remove reactivity of the serum for both HSB and human thymocytes. Similarly, absorption of anti-Ia serum with AMML cells removed all serological reactivity when this serum was tested on chronic lymphocytic leukemia cells or normal B-cells. These serological findings were confirmed by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis studies using radiolabeled antigens. Cells from an AMML patient were labeled with 125I using lactoperoxidase; both the TLAA and Ia antigens were precipitated from the resulting solubilized membrane preparation. Leukemic cells from one AMML patient and one patient with chronic myelogenous leukemia in blast crisis were studied for Ia and TLAA antigens with a double fluorescence technique. Over 80% of the cells showed dual fluorescence.