OBJECTIVE The aim of this study was to elucidate the permeability characteristics of the epithelium along the villus-crypt axis and investigate the effect of glucose transport on these characteristics along this axis. METHODS The disappearance rates of (14)C-mannitol and (51)Cr-EDTA or (3)H-inulin were determined as clearance (Cl(x)) from a recirculating perfusion system of the jejunal lumen in anesthetized rats. Net fluid transport was varied over a large range by exchanging mannitol with glucose in the perfusate solution and by inhibition of nervously mediated secretory processes with hexamethonium. The perfusion rate was 0.5 or 0.2 mL/min. RESULTS Cl(Man) enhanced significantly with increasing net fluid transport (secretion 8.50+/-1.88, to absorption 16.72+/-1.75 microL x min(-1) x g(-1)) and with glucose perfusates. Cl(Cr-EDTA) was constant irrespective of net fluid transport and was reduced to insignificant values at a perfusion rate of 0.2 mL/min. Cl(In) was not different from zero. CONCLUSIONS The absorbing apical part of the villus contains small pores (radius, <6 A) allowing passive transport via solvent drag of, e.g., monosaccharides, whereas the pores in the crypts are large (50-60 A) and inaccessible to the luminal content. The basal part of the villus contains medium-sized pores (10-15 A) through which no solvent drag occurs. Active glucose transport in the rat mainly increases the number of small pores accessible for passive transport, whereas the size of these pores seems to stay constant.