Enteroendocrine regulatory peptides may play an important role in the adaptation of small bowel mucosa, and it is likely that they act interdependently with neural and luminal stimuli. We assessed their action in rats by morphometric evaluation of enteroendocrine cells after heterotopic accessory small bowel transplantation (SBT), in which the graft is shunted off from the intestinal passage and is entirely deprived of neural connections, and after orthotopic SBT with normal intestinal passage. Sections of the jejunum and the ileum of the graft were immunostained with antibodies to cholecystokinin (CKK), neurotensin (NT) and vasoactive intestinal peptide (VIP). The amount and distribution of positive cells was assessed semiquantitatively. Three weeks after SBT in the heterotopic graft there was a marked decrease in CCK and NT positive cells and VIP positive fibres in the entire organ, compared with the controls. Histological examination revealed that villi and crypts had atrophied. After orthotopic SBT the number of CCK and NT positive cells increased and exceeded normal values by 20-40%. VIP positive fibres did not reach normal amounts. No mucosal atrophy was detected. These findings support the view that the intrinsic neurohormonal system is reestablished in the grafted small bowel and that enteroendocrine regulatory peptides may act as trophic factors that are responsible for adaptation after SBT.