To see whether intestinal permeability (IP) predicted relapse in Crohn's disease, we measured IP in 72 patients with quiescent Crohn's disease using the lactulose-mannitol test. The permeability index (lactulose/mannitol) was significantly higher in patients than in controls (0.046 [SEM 0.005] vs 0.018 [SEM 0.002], respectively). Patients were followed for 1 year after the test. 26 of the 37 patients with raised permeability, but only 6 of the 35 with normal permeability relapsed within 1 year after the test (p < 0.001). The sensitivity of the permeability test as a predictor for relapse was 81%. A significant correlation was found between the value of the permeability index and the probability of relapse (p < 0.01). These results show that increases in intestinal permeability precede clinical relapses in Crohn's disease and so are an indicator of subclinical disease. The measurement of intestinal permeability may lead to a better understanding of the pathogenesis of Crohn's disease.