The permeation of intravenously administered 51Cr-EDTA and [14C]mannitol to the perfused intestinal lumen was measured in anaesthetized rats together with the net intestinal fluid. Net fluid secretion was induced by cholera toxin or by intravenous infusion of vasoactive intestinal polypeptide (VIP). The plasma clearance of Cr-EDTA and mannitol was 0.9 +/- 0.1 and 1.4 +/- 0.2 microliters min-1 g-1 intestine during the control period prior to the secretion and the net fluid absorption was about 7 +/- 5 microliters min-1 g-1. Cholera toxin induced a net fluid secretion of about 30 +/- 7 microliters min-1 g-1 but the clearance did not rise but decreased significantly. The findings for VIP-induced secretion were similar. No indication of solvent drag was seen. Thus it is concluded that the fluid was secreted in channels which were smaller than the probes and we propose that the secreted fluid entered the intestinal lumen through the epithelial cells and not by the paracellular route. The decreased permeation of Cr-EDTA and mannitol from plasma to lumen during volume secretion suggest that there was a decreased mucosal permeability during the secretion. The decrease in permeability was consistent with a decrease in pore size. One explanation of the data is that the pore radius contracted from about 35 to 15 A during cholera if we assume a homogenous pore population. However, the data indicated that there was not a uniform size of the pore.(ABSTRACT TRUNCATED AT 250 WORDS)