Background. Neuropilins (NRPs) are characterized as co-receptors for VEGF. In this study, we determined the expression of NRPs, VEGF, and VEGFRs in pancreatic cancer cells and tissues as well as VEGF-induced cell proliferation. Methods. Human pancreatic cancer cell lines (Panc-1 and MIA PaCa-2), normal human pancreatic ductal epithelium cells (HPDE), and human umbilical vein endothelial cells (HUVECs) were cultured. Human pancreatic adenocarcinoma tissues were also studied. The expression levels of NRPs, VEGFRs, and VEGF were determined by real-time PCR and immunostaining. Cell proliferation was performed by [ 3 H]thymidine incorporation. Results. NRP-1 and NRP-2 were both expressed in Panc-1, HPDE, and HUVECs, but minimally expressed in MIA PaCa-2 cells. Panc-1 expressed 30 times higher NRP-1 mRNA than NRP-2 mRNA. NRP-1 mRNA in Panc-1 cells was 5.3 times higher than that in HPDE cells, but similar to that in HUVECs. NRP-2 mRNA in Panc-1 was similar to that in HPDE cells but lower than that in HUVECs. There was no expression of all three VEGFRs in all cell types except for HUVECs. However, the VEGF mRNA was detected in all cell types except for HUVECs. Immunoreactivity of NRP-1 was much higher than that of NRP-2 in Panc-1 and human pancreatic adenocarcinoma tissues, while VEGFRs were not detected. In response of VEGF 1 6 5 , [ 3 H]thymidine incorporation in Panc-1 was significantly increased by 61% (P < 0.01). Neutralizing antibody against NRP-1 significantly blocked VEGF-induced cell proliferation in Panc-1 cells. Conclusions. Pancreatic cancer cell line Panc-1 and adenocarcinoma tissues expressed high levels of NRP-1 and VEGF, but not VEGFRs, and exogenous VEGF significantly increased Panc-1 cell proliferation. Blocking NRP-1 significantly abolished the effect of VEGF on Panc-1 proliferation. These data suggest that direct interaction between VEGF and NRP-1 may be involved in pancreatic cancer pathogenesis.