Experience with young animals, animals administered certain hepatotoxins and animals with two-thirds hepatectomy suggests that tight junctional permeability is increased in states characterized by architectural remodeling in the liver. In this work we correlate changes in tight junctional morphometry induced by two-thirds hepatectomy with changes in biliary permeability assessed by sucrose and horseradish peroxidase permeation and by alterations in biliary outputs of anionic and cationic cholephilic probes. By freeze-fracture examination tight junctional strand counts, density and orientation parallel to canaliculi were all reduced 24 hr after two-thirds hepatectomy. Occasionally, strands were perpendicular to the canaliculi, creating an unobstructed communication between bile and intercellular spaces. These morphological changes correlated with increased sucrose and paracellular horseradish peroxidase access into bile, with reduced biliary outputs of low molecular weight and especially with cationic cholephilic probes. The data support an increased but still charge-selective permeability of the biliary tree, which was induced by two-thirds hepatectomy 24 hr before. Presumably, fixed intercellular connections (tight junctions and gap junctions) must be loosened or lysed to allow the architectural reorganization required by the hepatocellular regenerative process.