A new high pressure liquid chromatography (HPLC) method has been used to measure urinary sugar levels for the intestinal permeability test with cellobiose and mannitol (C/M test). Urinary specimens have been prepared by simple filtration through a Millipore membrane. The method is highly sensitive (minimal detectable concentration of urinary sugars = 0.01 mg/ml) and reproducible (coefficient variation between samples = 0.47% for cellobiose and 0.25% for mannitol). By this method a C/M test has been performed in a large series of gastroenterological patients. High values of mean urinary C/M percentage recovery ratio (C/M%) were found in 30 children with active gluten-sensitive enteropathy compared with controls (0.42 +/- 0.66 versus 0.014 +/- 0.005). In 44 treated celiacs and 34 children with chronic nonspecific diarrhea the mean C/M%s were 0.027 +/- 0.018 and 0.021 +/- 0.012, respectively. The results of this study confirm that the C/M test is a valuable investigation in the diagnostic studies of children with chronic diarrhea. The simple HPLC method described for the determination of urinary sugar levels should allow a wider diffusion of this test.