Proximal duodenum was perfused with various solutions and mucosal permeability assessed by measuring the clearance of 51Cr labelled ethylenediaminetetra-acetate (EDTA) from blood-to-intestinal lumen in anaesthetized rats. Net flux of fluid was determined by measurement of effluent weight changes. Perfusion of duodenum with 50 mM NaCl significantly increased fluid absorption but had no effect on EDTA clearance. EDTA clearance was unaffected by perfusion with 400 mM or 800 mM mannitol. Perfusion with 400 mM NaCl induced a sustained fluid secretion and a small but irregular increase (40%) in EDTA clearance. A significant 3.6-fold increase in clearance was obtained in response to perfusion of duodenum with deionized water. Similarly, perfusion with either 20 mM HCl or 50 mM ethyleneglycol-bis-(beta-amino-ethylether)-N,N'-tetraacetic acid (EGTA) significantly increased the EDTA clearance 3.3-fold and 2-fold respectively. Perfusion with a hypotonic HCl-solution (10 mM HCl + 40 mM NaCl) increased fluid absorption and the EDTA clearance. It is concluded that no positive linear relationship exists between luminal osmolality and 51Cr-EDTA movement across the mucosa. It is postulated that high luminal acidity or extreme hypotonicity increase the EDTA clearance by widening of and/or disruption of intercellular junctional structure.