We used recombinant-DNA techniques to determine the origin of polymorphonuclear leukocytes in patients with acute nonlymphocytic leukemia, at presentation, in remission, and in relapse. Studies using X chromosome-linked DNA polymorphisms strongly suggested that leukemic blast cells in this form of leukemia can differentiate in vivo to form mature granulocytes. Common chromosomal changes seen in blast cells, such as the addition of a chromosome 8 or the loss of a chromosome 7, were found to be present in the mature granulocytes of patients with leukemia. In addition, rearrangement of the immunoglobulin heavy-chain gene was detected in the polymorphonuclear leukocytes of one patient. Finally, we have observed the persistence of a single dominant hemopoietic clone in the granulocytes of 3 of 13 patients in complete remission. These findings demonstrate that recombinant-DNA probes can detect clonal populations of granulocytes in patients with acute nonlymphocytic leukemia, and provide further evidence that in some patients leukemic blast cells differentiate to form mature cells.