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We investigated intestinal permeability in healthy adult volunteers, and in patients with Crohn's disease, ulcerative colitis, idiopathic sprue and idiopathic hyperamylasemia by oral administration of 10 g low molecular weight polyethylene glycol (PEG-400) and quantitation of its renal excretion over the subsequent 6 hours by high performance liquid chromatography (gel permeation HPLC). The mean amount of PEG-400 excreted during the first 6 hours by the 12 patients with Crohn's disease (3.1 +/- 0.3 g, mean +/- SE) and the 8 patients with ulcerative colitis (2.6 +/- 0.3 g) was not significantly different from the amount excreted by the 24 healthy volunteers (2.9 +/- 0.1 g). The 3 patients with idiopathic sprue excreted significantly less (1.4 +/- 0.3 g, p less than 0.05) and the 3 patients with idiopathic hyperamylasemia significantly more (4.0 +/- 0.4 g, p less than 0.05) than the healthy controls. In conclusion, no alteration of intestinal permeability could be demonstrated in patients with Crohn's disease or ulcerative colitis. However, intestinal permeability was decreased in patients with idiopathic sprue and increased in those with idiopathic hyperamylasemia.