Down's syndrome (DS) is the most common factor predisposing to childhood leukaemia. Children with DS have a 10-to 20-fold excess risk of developing leukaemia (Table I)(Krivit & Good, 1957; Stewart et al, 1958; Wald et al, 1961; reviewed in Fong & Brodeur, 1987; Levitt et al, 1990; Robison, 1992; Zipursky et al, 1992; Avet-Loiseau et al, 1995). Roughly 1% of children with DS develop one or more of the following distinctive types of leukaemia:(i) a spontaneously regressing congenital or neonatal myeloproliferative disorder (TMD)(also known as transient myeloproliferative syndrome, congenital transient leukaemia, congenital leukaemoid reaction, transient leukaemoid proliferation and transient abnormal myelopoiesis);(ii) acute myeloid leukaemia (AML), usually acute megakaryoblastic leukaemia (AMKL)(or erythro/megakaryoblastic leukaemia before the age of 5 years); or (iii) common B-lineage acute lymphoblastic leukaemia (ALL)(for a review, see Zipursky et al, 1987; Robison, 1992; Avet-Loiseau et al, 1995). The current management strategy for these disorders, with few exceptions and considerable caution, is simple: in TMD,do nothing'; in AML,do less'; and in ALL,do more'. The rationale for this approach is the subject of this review.