Bone marrow and peripheral blood cells from three newborns with Down's syndrome and transient myeloproliferative disorders were cultured in vitro. In the methylcellulose semiliquid system, normal colony formation with maturation and differentiation into granulocytes and monocyte-macrophages were observed in all three patients. This is different from the growth pattern usually seen in acute nonlymphocytic leukemia. A maternal serum inhibitor of both normal allogeneic GM-CFU and blast cell growth was also demonstrated, but its role in pathogenesis is uncertain. Normal in vitro granulopoiesis may help to differentiate the transient myeloproliferative syndrome from congenital leukemia in newborns with Down's syndrome.