The surface antigen phenotype of 30 patients with the blast phase of chronic myeloid leukemia (CML) was determined using a panel of monoclonal antibodies recognizing differentiation antigens of normal myeloid, erythroid, megakaryocyte, and lymphoid cells. Ten patients' cells expressed a phenotype corresponding to an immature myeloid cell and were felt to have "myeloid" blast crisis. None of these myeloid leukemias were TdT+ or responded to vincristine (V) and prednisone (P). Eleven patients expressed a phenotype similar to acute lymphoblastic leukemia cells and probably reflect maturation to an early B lymphocyte. All of these "lymphoid" leukemias were TdT+, and 67% of evaluable patients had a complete response to V and P. One leukemia had the phenotype of an erythroleukemia, one patient's cells expressed the phenotype of megakaryoblastic leukemia, and one leukemia had populations of both myeloid and lymphoid blasts. Six leukemias did not express surface markers characteristic of any lineage and were termed "undifferentiated." This group was heterogeneous with respect to TdT expression, but no patient had a complete response to V and P. Determination of surface antigen phenotype in CML blast crisis thus provides clinically useful information for the structuring of treatment protocols.