Neonates with Down's syndrome may develop a transient myeloproliferative disorder (TMPD) which on presentation is indistinguishable from acute leukemia, with the difference manifest only on follow-up. The clinical course is one of spontaneous remission in TMPD and relentless progression in leukemia. We describe a Down's neonate presenting with hyperleucocytosis and circulating blasts which were positive for CD34, myeloid (CD33), megakaryocytic (CD41, CD42b, CD61), and T-lineage (CD3, CD7), but not B-lineage, associated antigens. Clonal rearrangement of the T-cell receptor beta (TCR beta) gene was found, with the immunoglobulin heavy chain gene in germline configuration, showing the disease to be a clonal proliferation of a multipotential stem cell involving the myeloid and T lineages. Dual-colour flow cytometric DNA ploidy analysis of CD41 positive blasts showed initially a predominant 2N population, but polyploidization to 6N and 8N cells was found on follow-up, concomitant with a progressive decrease in circulating blasts, suggesting maturation of the abnormal clone and a provisional diagnosis of TMPD. This was shown by the eventual resumption of normal haemopoiesis with the disappearance of blasts and the clonally rearranged TCR beta gene.