A series of monoclonal antibodies reactive with normal myeloid cells at different stages of differentiation (anti-MY4, -MY7, -MY8, -Mo1, -Ia) were used to characterize the leukemic cells of 70 patients with acute myeloblastic leukemia (AML). Sixty-two of the leukemias expressed a phenotype corresponding to a recognizable immature normal myeloid cell. These 62 cases could be divided into 4 phenotype groups, corresponding approximately to the normal CFU-C (group I, 21%), myeloblast (group II, 26%), promyelocyte (group III, 8%), and promonocyte (group IV, 45%). Morphological subtyping of these leukemias tended to agree with the immunologic phenotype, particularly with more “differentiated” morphological subtypes, such as acute monocytic leukemia or acute promyelocytic leukemia. However, each phenotype group contained more than one morphological type of AML, indicating that the level of differentiation of the surface membrane of AML cells may not always be concordant with morphology. The phenotype groups were also analyzed with respect to cytochemical staining patterns, age, the presence of Auer rods, and complete remission rates. Statistically significant differences among the groups were noted in the distribution of myeloperoxidase staining, nonspecific esterase staining, and Auer rods. The complete remission rates varied from 60% (groups III and IV) to 88% (group II). These results suggest that surface marker analysis in AML may be used as a highly reproducible classification system that will provide additional information about the leukemic cells in conjunction with morphological analysis.