The aim was to assess the roles of gut hormones and immune dysfunction in irritable bowel. In Study I, rectal mucosal samples examined blindly showed no histological evidence of inflammation in 16 irritable bowel patients compared to 17 healthy controls. The proinflammatory mediators interleukin-1beta and prostaglandin E2 also failed to show evidence of inflammation. Vasoactive intestinal peptide was elevated in irritable bowel (P = 0.01), but substance P, calcitonin gene-related peptide, and somatostatin levels were similar to control values. In Study II, 30 irritable bowel patients had elevated (P = 0.002) plasma concentrations of vasoactive intestinal peptide compared to 30 controls, and peptide levels were unrelated to whether the patient's predominant bowel habit was constipation, diarrhea, or both in alternation. In conclusion, no evidence of inflammation was detected in irritable bowel patients, but elevated vasoactive intestinal peptide concentrations were observed in both studies and might represent a potential diagnostic tool for irritable bowel syndrome.