Intestinal tight junction function is thought to be of importance in the pathogenesis of various diseases. The regulation of uptake of macromolecules via the tight junctions is largely unknown. Effects of luminal sodium caprate (10 mM), a dairy product constituent, and cytochalasin B (30 microM), were studied in rat ileum in vitro in Ussing chambers. Both agents caused a reversible fall in potential difference and increased [51Cr]EDTA permeability. In addition, sodium caprate induced increased permeability to polysucrose (15,000 daltons) and opening of the tight junctions as visualized by transmission electron microscopy. Dose-response patterns suggested mainly dose-dependent differences between the agents. Confocal laser scanning microscopy suggested paracellular permeation of polysucrose. Luminal sodium caprate, a food constituent, can increase tight junction permeability, allowing passage of macromolecules, without affecting epithelial viability. Increased permeability to medium-sized molecules does not necessarily coincide with increased paracellular uptake of protein-sized molecules.