Blood and bone-marrow smears from adult patients with acute leukemias were stained for esterase reaction, consecutively with naphthol AS D-chloracetate (chloracetate esterase) followed by alpha naphthyl butyrate (nonspecific esterase). The two substrates were, respectively, granulocyte- and monocyte-specific. By this method three subgroups of acute nonlymphocytic leukemias could be distinguished. Leukemic cells may be positive for either chloracetate esterase or nonspecific esterases, and the authors believe these two subgroups represent "true" granulocytic and "pure" monocytic leukemias. In a third group, leukemic cells contained both esterases in the same cell, and it is believed this group may represent "true" myelomonocytic leukemias. In the majority of patients in this group, leukemia evolved from a preleukemic phase. When only Romanowsky-stained smears are used, the monocytoid feature and absolute elevated monocyte counts in acute granulocytic leukemia may lead to an erroneous diagnosis of the leukemia as acute myelomonocytic leukemia. This happened in five of the 13 cases in the study. The presence of granulocyte- and monocyte-specific esterases in a single cell supports the concept of a common origin of granulocytes and monocytes. The authors conclude that the combined esterase reaction can distinguish among acute granulocytic leukemia, acute monocytic leukemia, and acute myelomonocytic leukemia.