Gastrointestinal activity is controlled primarily by the enteric nervous system through the release of different neurotransmitters, many of which are neuropeptides. The endogenous opioid peptides play an important role in regulating intestinal function and opioid peptides have been localised in enteric neurones of the human gastrointestinal tract (Kromer, 1988) and also in neuroendocrine (NE) cells within the mucosal crypts (Ahlman & Nilsson, 2001). Inflammatory bowel disease (IBD; Crohn’s Disease and ulcerative colitis (UC)) is a condition of unknown aetiology that seriously affects gut function and it has been proposed that neuronal changes may contribute to the pathophysiology of IBD (Shanahan, 1998). In this investigation we have used immunhistochemistry to observe the distribution of the opioid peptide, [Met]enkephalin in the bowel wall of patients with IBD and of non-inflamed “normals”.Archival paraffin embedded sections of diseased tissues and formalin fixed fresh specimens of “normal” tissue were obtained from Glasgow Royal Infirmary with informed patient consent and local ethical approval. Standard ABC techniques were employed and results visualised using light microscopy. Anti-[Met]enkephalin (Affiniti, UK) antibody was used at 1:800 dilution.[Met]enkephalin-like immunoreactivity was observed in the myenteric nerve plexus and in neurones throughout the muscularis externa in both inflamed and non-inflamed specimens, however, no significant difference in staining intensity was apparent. There was no evidence of immunoreactivity in the submucosa but [Met]enkephalin-like immunoreactivity was clearly present in the mucosal crypts. In all Crohn’s disease specimens (n=5), intense staining was observed in numerous cells within the mucosa; these cells are most probably NE cells. In UC specimens, [Met]enkephalin-like immunoreactivity was also localised to these mucosal crypt cells in 6 out of 7 specimens, with varying degrees of intensity but in fewer cells than observed in Crohn’s disease. In only 2 out of 5 non-inflamed specimens, weak immunoreactivity was seen in these NE-like cells. In conclusion, there appear to be alterations in the pattern of [Met]enkephalin-like immunoreactivity in the mucosal crypts of patients with IBD. These observations are in agreement with El-Salhy et al., (1997), who have shown perturbations in the numbers of NE cells in IBD. Experiments are ongoing to determine if this mucosal immunoreactivity is indeed found exclusively in NE cells.