Immunophenotyping has become common in the diagnosis and classification of acute leukemias and is particularly important in the proper identification of cases of minimally differentiated acute myeloid leukemia (AML-M0). To evaluate the immunophenotype of adult AML, 106 cases were studied by cytochemical analysis and by flow cytometry with a panel of 22 antibodies. The results were compared with the French-American-British (FAB) Cooperative Group classification, as well as with available cytogenetic data on each case. CD45, CD33, and CD13 were the most commonly expressed antigens (97.2%, 95.3%, and 94.3%, respectively). Lymphoid-associated antigens were expressed in 48.1% of cases. CD20 was the most commonly expressed lymphoid antigen (17%), although often expressed in only a subpopulation of leukemic cells, followed by CD7 (16%), CD19 (9.8%), CD2 (7.5%), CD3 (6.7%), CD5 (4.8%), and CD10 (2.9%). Some immunophenotypes correlated with FAB type, including increased frequency of CD2 expression in AML-M3; lack of CD4, CD11c, CD36, CD117, and HLA-DR expression in AML-M3; increased frequency of CD20 and CD36 expression and lack of CD34 expression in AML-M5; increased frequency of CD5 expression in AML-M5a; and increased frequency of CD14 expression in AML-M5b, when compared with all other AMLs (P < .05). When compared with AML-M5b, AML-M5a demonstrated a lack of CD4 expression and a high frequency of CD117 expression. Complete morphologic and cytogenetic agreement between AML-M3 and t(15;17) was present, and four of five cases of AML-M4Eo demonstrated inv(16). The remaining case of M4Eo was characterized by a 6;9 translocation, and two other inv(16) cases were not classified as M4Eo. Expression of CD2 was present in two t(15;17) cases and in one inv(16) case, but expression of this antigen was not restricted to AML cases with these karyotypic abnormalities. Similarly, expression of CD19 was not specific for t(8;21) AML. All t(8;21) leukemias demonstrated M2 morphology. With the exception of M3, M4Eo, and a subgroup of M2 leukemias, the FAB classification does not appear to define cytogenetically distinct disease groups in adult AML. Immunophenotypically distinct profiles were identified in the M3 and M5 morphologic groups of the FAB classification. Immunophenotyping studies are helpful in the determination of myeloid lineage. In general, however, they are not sufficiently specific alone to be useful in precisely identifying either FAB or cytogenetically defined disease subtypes.