Therapy with vincristine and prednisone (VP) has produced remissions in 30% of patients with chronic myelogenous leukemia in blast transformation (CML-BT). The possibility that therapy with VP can adversely affect the production of mature granulocytes in this setting has not been appreciated, as these drugs are generally considered free of myelotoxicity. In this report we review eight courses of VP administered to three patients with CML-BT. Granulocytopenia developed following all five courses in which granulocyte counts were normal prior to therapy; granulocytopenia worsened in two of three courses in patients who were granulocytopenic prior to therapy. Progressive leukemia in the marrow was excluded as a cause of granulocytopenia. It is important to recognize that VP therapy rather than disease progression may be a cause of granulocytopenia in CML-BT.