Karyotypic evolution was found in 13 of 42 (31%) patients who were examined serially; if only those patients who were examined during successive stages of active leukemia were included, karyotypic evolution was revealed in 13 of 21 (62%). A further 6 patients showed multiple cytogenetic clones when leukemia was diagnosed. We did not find nonrandom chromosome involvement in the karyotypic changes, reported by others, notably trisomy #8. Our data for all patients who showed cytogenetic clones at some stage of their disease suggested that clones occurred with a higher incidence and arose earlier in patients with myeloblastic leukemia than in patients with myelomonocytic and monocytic leukemia. Patients showing karyotypic evolution tended to have longer than average survivals and to have had an abnormal karyotype when leukemia was diagnosed. The mode of preparation of hematologic samples, whether direct or cultured, has a bearing on karyotypic findings and could influence studies of karyotypic evolution.