Cytogenetic studies, using improved short-term culture techniques, were performed on 64 patients with acute leukemia to determine the incidence and kinds of clonal karyotypic changes detectable with this newer methodology. An adequate number of analyzable mitoses was obtained from 59 patients. Clonal chromosomal alterations were found in 88% (52 of 59) of patients, as compared to approximately 50% in previous studies of acute leukemia in which conventional techniques were used. From our series, abnormal karyotypes were detected in 37 of 44 (84%) cases with primary acute nonlymphocytic leukemia, all 5 with secondary acute nonlymphocytic leukemia, and all 10 with acute lymphoblastic leukemia. Among the entire group of patients, several recurrent abnormalities were observed, e.g., -7 in eight cases, +8 in seven cases, t(15;17) in four cases, and t(8;21) or a variant of this translocation in four cases. In five patients, the only abnormality was a rather subtle structural rearrangement (e.g., tiny deletion). Five other patients had clonal changes which were found in less than 10% of the mitoses examined in each case. Our results indicate that most patients with acute leukemia, both acute nonlymphocytic leukemia and acute lymphoblastic leukemia, have clonal chromosome abnormalities associated with their disease.