Morphological and functional changes were examined in the upper jejunum and terminal ileum of 18 patients suffering from Crohn's disease. Intestinal permeability, biochemical determination of enzymatic activities, and morphologic evaluation of the severity of the lesions were evaluated. Ulcerative colitis and irritable bowel syndrome patients served as controls. We found abnormal lactulose-mannitol tests in all patients with active Crohn's disease. Permeability changes correlated with increased crypt cell proliferation, as indicated by thymidine kinase activity. A significant reduction in brush border enzyme activities was seen in the terminal ileum, but no significant change was observed in the unaffected upper jejunum. The number of mast cells was increased in the diseased ileum. We conclude that the site of inflammation and the healing capacity of the epithelium are important in determining functional and biochemical abnormalities in active Crohn's disease. Changes may be dependent on the type and number of immune cells involved in the inflammatory process.