Eighty-four patients underwent allogeneic or syngeneic bone marrow transplantation as therapy for chronic myelogenous leukemia (CML) during a 5-year period at The Johns Hopkins Oncology Center. We describe the karyotype at relapse in 19 patients who were Ph chromosome positive (Ph+) at diagnosis. Eighty-four percent of patients demonstrated clonal and/or nonclonal chromosome abnormalities in addition to the t(9;22)(q34;q11) at first detection of relapse or later during relapse. These abnormalities included: Ph plus additional clonal abnormalities (three patients), Ph plus nonclonal abnormalities (five patients), Ph plus additional clonal and nonclonal abnormalities (eight patients). Three patients had only the original Ph+ clone. The additional chromosome abnormalities were primarily structural, and entirely different from those most frequently observed during karyotypic evolution in conventionally treated CML. Chromosome 1 was most frequently involved, with 1q32 being the location of three clonal and two nonclonal abnormalities. Other sites included 6p21-22 (the site of two clonal abnormalities), 7p21-22, and 10q21 (the site of two clonal and one nonclonal abnormality each). Chromosomes 5 and 7q, regions of frequent involvement in acute nonlymphocytic leukemia that follows chemotherapy for other malignancies, were infrequently involved. The clinical significance of these additional abnormalities remains undetermined at this time.