Aim: Investigate the importance of paracellular transport of water and solutes during physiological and pathophysiological conditions. Methods: The transport of small water-soluble inert permeability markers, was studied in jejunum and colon in anesthetized rats and cats during normal conditions and during exposure to cholera toxin (CT) and deoxycholic acid (DCA). The intestinal segments were isolated with intact vascular supply and connected to a perfusion system. The appearance and the disappearance rate of the probes into and from the intestinal perfusate in the presence and absence of 30 mM glucose as well as net fluid transport (NFT) were determined. The involvement of nerve effects was tested by the nicotinic receptor inhibitor, hexamethonium. Results: In the rat and cat small intestine there was a correlation between NFT and mannitol, but not of Cr-EDTA and inulin disappearance rates. Glucose increased NFT and transport of mannitol in both species but in rat this effect was larger than the increase in NFT. In colon only the disappearance rate of urea was significant while the appearance rate of the probes in the proximal colon was similar while in the distal colon it was lower compared to jejeunum. CT decreased while DCA increased the appearance rates. The DCA effect was inhibited by hexamethonium. Conclusions: The epithelium of small intestine and colon is a heteroporous membrane, containing large pores in the crypts (radius 50-60Å) with a successively decreasing pore size as the enterocytes mature and differentiate during their movement towards the villus tips/surface epithelium (here radius 6/3Å). The small pores, localized in the absorptive area of the epithelium, seems only to allow significant transport of water and electrolytes and is not affected by glucose transport. The luminal content have no access to the crypts and the crypt fluid secretion are reabsorbed in the villi/surface epithelium implying that NFT is the difference between large in and out fluxes of water. CT induced fluid secretion occurs transcellularly. The nerve reflex increasing epithelial permeability activated by DCA is not an axon reflex and do not involve NO or mast cells.