Although a neural crest origin has been proposed for pancreatic beta cells, these cells are known to possess many similarities with neuronal cells. These similarities give rise to the hypothesis that undifferentiated neural crest cells can be transformed into beta cells. The objective of this study was to compare beta-cells and undifferentiated neural crest cells with respect to c-Fos immunoreactivity (c-Fos-IR), which plays a crucial role in certain cellular and biological processes and is used as a neuronal activity marker. For the purpose of the study, c-Fos-IR has been analysed by immunohistochemical methods in rat pancreatic beta cells, pulpal undifferentiated ectomesenchimal cells (PUECs) that are known to have a neural crest origin, and in small intestine fibroblasts which do not have a neural crest origin, in formaline-fixed, paraffin-embedded sections. There were no significant differences between beta-cetts and PUECs in c-Fos-IR (p > 0.05), but there was a highly significant difference between fibroblasts and the other two type of cells (p < 0.001). These results give rise to and support the suggestion that PUECs can be transformed into beta-celts. (C) 2004 Elsevier Ltd. All rights reserved.