An altered small bowel permeability may be implicated in the pathogenesis of Crohn's disease. Intestinal permeability, using polyethylene glycol 400 (PEG 400) as the orally ingested probe, was assessed in 45 patients with Crohn's disease (ileal N = 14, ileocolonic N = 9, colonic N = 10, postresection N = 12), 20 first-degree relatives, and 31 controls. PEG 400 excretion was measured using a direct injection HPLC method, and results are expressed as percent of dose recovered in urine (median and range). No quantitative differences in the recovery of PEG-400 were found [Crohn's patients 21.9% (6.1-39.9), relatives 23.7% (4.9-39.9), controls 25.0% (4.5-39.7)]. In all groups, the composition of ingested and recovered PEG-400 was similar and no selective permeability to any molecular weight species was found. Disease site did not influence probe recovery [ileal 23.8% (7.7-30.6), ileocolonic 22.6% (14.4-33.8), colonic 27.8% (9.5-33.5)]. Resected patients had significantly lower PEG-400 recovery [18.8% (8.1-39.9)] than nonresected patients [23.5% (6.1-33.8%) P less than 0.02]. The data suggest either that altered intestinal permeability is not a factor in Crohn's disease or that PEG-400 is not a suitable probe.