The leukemic cells from 15 cases of Philadelphia chromosome-positive blastic leukemia were immunophenotyped by the alkaline phosphatase anti-alkaline phosphatase (APAAP) immunocytochemical technic using nine monoclonal antibodies (MoAb) reactive with various myeloid or lymphoid antigens. On the basis of morphology, cytochemistry, terminal deoxynucleotidyl transferase (TdT) reactivity, and electron microscopy, five of the cases had been classified as lymphoid; eight, myeloid; one, mixed myeloid-lymphoid; and one, undifferentiated. The blasts from all five lymphoid cases were reactive with lymphocyte differentiation antigen MoAb, and four of five reacted with MoAb to anti-common acute lymphoblastic leukemia-associated antigen (CALLA) (BA3). The blasts from all eight myeloid cases were reactive with MY7, a marker of myelomonocytic differentiation. Some of the blasts from three of the eight myeloid cases reacted with HP1-1D and AP3, markers of the megakaryocytic differentiation; megakaryocyte differentiation was confirmed by electron microscopy. In the case classified as mixed myeloid-lymphoid, the blasts showed morphologic and immunophenotypic heterogeneity; ultrastructural studies demonstrated lymphoid, basophil, and erythroid differentiation. The blasts from the case classified as undifferentiated were immunophenotypically heterogeneous. In all cases in which the leukemic cells were also immunophenotyped by flow cytometry, the results correlated well with those obtained by the APAAP technic. The APAAP technic is a reliable method for immunophenotyping leukemias. Advantages of this method include its applicability to routinely prepared blood and bone marrow smears and cytocentrifuge preparations, lack of endogenous peroxidase background staining, and a permanent record.