Three Down's syndrome patients with transient myeloproliferative disorder were studied for clonality of the proliferating blast cells using the X chromosome-linked polymorphic gene phosphoglycerate kinase, immunoglobulin heavy chain (IgH) gene and T-cell antigen receptor (TCR) (beta, gamma, delta) genes. None of the three cases showed rearrangements of IgH, TCR beta, gamma, or delta genes, indicating the non-lymphoid nature of the proliferating blast cells. The X chromosome inactivation pattern showed that the cells in the blast population in all of the three cases of transient myeloproliferative disorder were clonal. These data suggest that at least some of this disorder can be due to a spontaneously regressing clone of malignant cells.