Pancreatic carcinoma is one of the most aggressive human malignancies. The aggressive and highly metastatic behaviour of pancreatic carcinoma may partly be attributable to the autocrine and/or paracrine interactions involving altered expression of neurotrophin growth factors and their corresponding receptors. The aim of the present study is to investigate the expression pattern and function of the p75 NGFR protein in pancreatic cancer cell lines and tumours to explain the phenomenon of perineural invasion in pancreatic cancer.The expression of p75 NGFR in 137 pancreatic adenocarcinoma samples and the corresponding adjacent pancreatic samples was examined immunohistochemically using the EnVision Plus System. Then we examined the in vitro chemotaxis behaviour of cancer cells transfected with p75 NGFR plasmid to nerve growth factor (NGF).Immunostaining for p75 NGFR was weak or absent in both normal pancreata and pancreatic carcinoma tissues; however, the immunostaining was relatively weaker in the pancreatic carcinoma tissues than in the normal pancreata. It is interesting to note that p75 NGFR expression in the cancer tissues was positively correlated with the degree of perineural invasion (χ 2 =32.94, P<0.01). The chemotaxis ability of the p75 NGFR -transfected pancreatic cancer cells to NGF was significantly stronger than that of the non-transfected or vacant vector transfected cells (P<0.01).Our findings indicate that p75 NGFR expression may be involved in the perineural invasion of pancreatic cancer cells, and the mechanism might be through mediating the chemoattraction of cancer cells for neural tissues.