Thirty patients in the blastic phase of chronic granulocytic leukemia were treated with a combination of vincristine, 2.0 mg/sq m weekly, and prednisone, 60 mg/sq m orally each day. Remission was achieved in nine patients (30%), six of whom had a complete remission, and three had a good partial remission. The survival of responding patients was significantly improved over the nonresponders. Cytogenetic studies were performed on all patients in the chronic phase of the disease, and in 28 during the blastic phase. All were Philadelphia chromosome-positive throughout their course. Aneuploidy developed in 68% of the patients entering the blastic phase. Complete hematologic remission was accompanied by disappearance of aneuploid blast cell lines in the five patients in which they were detected, with return of the chromosomal constitution to that which characterized the chronic phase of their disease. Hypodiploidy in blastic transformation of CGL appeared to predict for a favorable response to vincristine and prednisone. Subsequent relapse of the disease in previously remitted patients was associated with further degrees of aneuploidy, suggesting clonal evolution of a resistant cell line.