Modifications of the electrofocusing patttern, immumological reactivity and kinetic properties of glucose-6-phosphate dehydrogenase [G-6PD] were studied in malignant blood cells of various leukemias and myeloproliferative disorders. Granulocytic G-6PD forms with decreased isoelectric points were found in all acute myeloid leukemias and erythroleukemias, and in most of the chronic granulocytic leukemias and myelofibrosis. Granulocytic G-6PD from patients with polycythemia vera was always normal. Leukemic lymphocyte or lymphoblast G-6PD was identical to that from normal lymphocytes. The ratio of enzymatic activity to immunological reactivity ( = molecular specific activity) was decreased in the myeloblasts of 2 patients with acute myeloid leukemia, and in the erythroblast-rich cellular fraction of a patient with erythroleukemia. In these cells the decrease of molecular specific activity was parallel to the alteration of the electrofocusing pattern of G-6PD. The enzymatic forms with decreased isoelectric point also exhibited an altered affinity for G-6PD. These modifications are posttranslational alterations of the neosynthesized G-6PD, since this enzyme is a single molecule, coded by the same gene in all tissues. They seem to correspond to an accelerated molecular aging due to an increase concentration of G-6PD modifying factors. The significance of such an increased concentration of these G-6PD modifying factors in malignant cells is discussed.