Ultrastructural cytochemical changes occurring during the blast phase of chronic myelocytic leukemia (CML) are described. Normal developing promyelocytes contain myeloperoxidase (MPO) -positive rough endoplasmic reticulum, nuclear envelope, and Golgi apparatus. All secretory granules of normal promyelocytes are also MPO-positive. In this study we have found abnormal promyelocytes with MPO-positive as well as MPO- negative secretory granules in blast phase CML patients which contrast with the normal pattern of MPO distribution in most CML patients not in the blast phase or in nonleukemic controls. Alkaline phosphatase activity was found in the nuclear envelope of blasts and promyelocytes of one of the blast transformation patients who had a markedly increased leukocyte alkaline phosphatase score. The cytochemical changes in the distribution of MPO suggest that immature leukemic cells may alter their patterns of secretory granule production. Such processes may reflect the emergence of an abnormal clone of cells during the blastic transformation of CML.