In the small bowel of patients with cystic fibrosis, primary defects involving both chloride transport and mucus secretion have been demonstrated, but there is no general consensus about the morphologic counterpart of functional and biochemical abnormalities. We have studied the intestinal mucosa in a group of patients with cystic fibrosis and gastrointestinal symptoms with the aim of evaluating whether the intestinal mucosa is normal as previously described. The results showed that the small bowel involvement is characterized by a typical pattern of lesions with preservation of the mucosal architecture and abundant mucus at the surface. In the villi, the absorbing cells were generally well preserved, but unusual features were found in the apical portion of the goblet cells, which formed sacks containing mucus droplets. Similar sacks were also found detached from the goblet cells. Aspects of degeneration were present in the upper portion of the crypts where elements with an extensive vacuolization of the cytoplasm and swelling were detectable. This study demonstrates that in patients with cystic fibrosis the ultrastructure of the small bowel mucosa is not normal as previously described, but that an ultrastructurally detectable enteropathy exists. This enteropathy seems to be localized mainly in sites where molecular biology studies described the highest expression of cystic fibrosis transmembrane conductance regulator.