Small intestinal permeability to horseradish peroxidase (HRP) was assessed in jejunal biopsies of malnourished children. Clinical examination, intestinal function (D-Xylose test), and the histological appearance of the mucosa were assessed in 14 children during the malnutrition phase and in eight children after 3 months of nutritional rehabilitation. Macromolecular permeability was evaluated by measuring transepithelial HRP fluxes from mucosa to serosa (JHRPms) using Ussing chambers. Intact HRP transport, i.e., nondegraded protein transport, was measured by enzyme assay, and tritiated HRP was concomitantly used to measure intact and degraded HRP fluxes (J[3H]HRPms). Electrical parameters (short-circuit current, potential difference, and ionic conductance) were also recorded. Transepithelial HRP fluxes were significantly higher during malnutrition (JHRPms = 8.85 +/- 1.44; J[3H]HRPms = 77.11 +/- 10.66 pmol X h-1 X cm-2) than in the same children after 3 months of nutritional rehabilitation (JHRPms = 2.94 +/- 1.10; J[3H]HRPms = 22.93 +/- 8.15 pmol X h-1 X cm-2). The total ionic conductance, which is an index of paracellular permeability, did not change significantly. Calculated intratissue degradation of the protein did not appear to alter during malnutrition. These results point to a clinical situation in which malnutrition with diarrhea in children is associated with increased intestinal permeability to macromolecules by a mechanism not related to any paracellular leak of the protein, but rather to increased transcellular absorption.