The presence of micromegakaryocytes in the blood and bone marrow of humans during the preleukemic phase of acute and chronic myelogenous leukemia and myelomonocytic leukemia is well documented [I, 4, 5, 7, 8, 10, 15), and it has been suggested that it is the single most typical abnormality suggesting a subsequent course towards overt leukemia (6). Three adult purebred beagles that died with myelogenous leukemia during continuous whole-body exposure to 2.5 roentgens/22-hour day of 6OCO gamma irradiation had micromegakaryocytes and megakaryoblasts in the peripheral blood three to ten weeks before leukemic myeloblasts were observed in buffy coat preparations. The cells of interest were 6 to 30 JLm in diameter, mono-, or binucleated, with round or oval nuclei, indistinct nucleoli, and they had a high nuclear/cytoplasmic ratio (fig. I). Many cells had cytoplasmic blebs (fig. 2). Cytochemical characterization revealed strong positive staining for both acetylcholinesterase, and a-naphthyl acetate esterase, as well as abundant glycogen with the periodic acid-Schiff stain. The cells were negative with Sudan black, and no detectable myeloperoxidase or naphthol AS-D chloroacetate esterase activity was seen. Other hematologic abnormalities observed during this preleukemic period included progressive refractory anemia, occasional nucleated red blood cells, anisopoikilocytosis, monocytosis, giant platelets, and a left shift to metamyelocytes. Over the same period, bone marrow preparations from iliac crest aspirates and rib biopsies revealed granulocytic hyperplasia with a moderate left shift but without an excess of myeloblasts. There was also erythroid depletion, and increased numbers of mono-, bi-, and multinucleated megakaryocytes (fig. 3). Ultrastructural characterization clearly indicated the cells to be micromegakaryocytes and megakaryoblasts. Even in the most immature cells, the cytoplasm contained both dense serotonin granules and the characteristic a (bull's-eye) granules, indicating their megakaryocytic lineage (fig. 4). Although the majority of micromegakaryocytes showed dysgenesis of the demarcation membrane system, the cytoplasm did contain smooth, membranous vesicular sacs of a rudimentary demarcation membrane system (fig. 4) and in a few cells there were flattened, laminar cisternae of the demarcation membrane system with peripheral formation of dystrophic (i.e., agranular, giant) platelets. Terminally, the dogs were severely anemic (0.94, 1.10, and 1.70 X 10 red blood cells/ul), and thrombocytopenic (5.0, 7.5, and 90.0 X 10 Total leukocyte counts were 11.5, 14.8, and 57.1 X 10/ JLI, respectively. The terminal peripheral blood differential leukocyte count showed a marked left shift (17%myeloblasts) in only one dog. However, bone marrow imprints obtained at necropsy from sternum, rib, and femur showed, in all dogs, a granulocytic hyperplasia with maturation defects and myeloblast counts of 21.0, 11.0, and 35.5% of the total granulocytic series. In all dogs there was a paucity of erythroid elements and in only one dog were there a few remaining megakaryocytes.