Neuropilin-1 (NRP-1) is a novel receptor of vascular endothelial growth factor (VEGF) and expressed in endothelial cells and tumor cells. The role of NRP-1 in the growth and progression of leukemia is unknown. Here we studied the mRNA expression and effect of NRP-1 in leukemic cells. Our results showed that NRP-1 mRNA was expressed in six of seven leukemic cell lines and primary leukemias derived from all 24 patients with acute myeloid leukemia (AML). Reduced NRP-1 expression by RNA interference led to a decrease of VEGF-mediated mitogenic and migration responses in acute myeloid leukemic cell line HEL. Increased NRP-1 expression was directly correlated with the blast percentage in both peripheral blood and bone marrow of AML patients. Our data demonstrated that a higher level of NRP-1 mRNA was expressed in leukemias and NRP-1 promoted proliferation and chemotaxis of leukemic cells in response to VEGF. Inhibition of NRP-1 functions may provide a new therapeutic strategy for treatment of AML.