The factors regulating the differentiation of the endocrine cells of the pancreas are still unknown. In previous studies, we have demonstrated that, like neurones, various beta-cell lines express functional neurotrophin receptors. Moreover, Trk-A, the nerve growth factor (NGF) high-affinity receptor, is expressed in vivo in mature rat islets and early during development in the pancreatic ductal network that represents the source of putative stem cells. Rat pancreatic AR42J cells possess both exocrine and neuroendocrine properties. Recent studies have shown that these cells can differentiate either into acinar cells or into insulin-expressing cells. In this study, we demonstrate that AR42J cells, in common with the embryonic ductal cells, do express Trk-A. Moreover, on treatment with NGF, Trk-A is phosphorylated and early responsive genes such as NGFI-A, c-fos and c-jun are induced. These results clearly show that the Trk-A receptor expressed in AR42J is functional. AR42J cells provide a model system with which to study the role of NGF in the development of the pancreatic cells.