This article describes three patients with megakaryoblastic leukemia, in whom the blast cells were identified as megakaryoblasts by the platelet peroxidase (PPO) reaction. More than 70% of the blasts in these patients were positive for the PPO reaction. Ultrastructurally, acid phosphatase activity in the megakaryoblasts was detected in the nuclear envelope, the endoplasmic reticulum, and in a few granules, but not in the Golgi cisternae. Some blast cells were identified by immunofluorescence or immunoalkaline phosphatase, using monoclonal antiplatelet glycoprotein IIb/IIIa antibody. In one patient, most of the blasts were positive for anti-HLA-DR monoclonal antibody. The possible order of the appearance of markers in the maturation of the megakaryocytic cell lineage is postulated, based on the data from the present cases and those previously reported. PPO activity appears in very immature cells, which retain Ia-like antigens. Platelet-specific glycoprotein IIb/IIIa is seen in immature cells that are only recognized by PPO activity.