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Background: An increased prevalence of irritable bowel syndrome (IBS) and disturbances in cardiac and blood pressure reflexes have been described in patients with Crohn's disease (CD) and ulcerative colitis (UC). These features could be due to abnormalities in the gastrointestinal neurotransmission. The aims of this study were to examine whether histopathologic changes in the enteric nervous system correlate with disturbances in cardiac and blood pressure reflexes and the occurrence of IBS- and dyspepsia-like symptoms in these patients. Methods: Thirty patients with CD and UC with bowel resection were examined by deep-breathing and orthostatic tests. The resection specimens were evaluated histologically regarding visceral neuro- or myopathy. All medical records were studied for treatment and clinical course. Results: Ganglioneuritis was observed in 11 of 19 patients with CD and in 5 of 11 with UC. Only patients with CD had ganglioneuritis in the small intestine. Moreover, in CD the interstitial cells of Cajal (ICCs) in the small bowel showed atrophy and vacuolar degeneration, along with a reduced number of cells (P = 0.005). In UC the colonic ICCs were hyperplastic (P = 0.05) without signs of degeneration. The indices of deep-breathing and orthostatic tests were impaired, except in CD with ganglioneuritis, who showed normal test values. There were no correlations between histopathologic alterations versus IBS and dyspepsia. Conclusions: Visceral ganglioneuritis and pathologic ICCs were observed in patients with CD and UC. However, these histopathologic abnormalities could not be related to the clinical or autonomic features of the disease.