In the present study, we addressed the problem whether sympathoadrenal mechanisms could influence the paracellular permeation of macromolecules from the lumen to the lamina propria of the small intestine. Experiments were conducted with rats that were anesthetized with ether for 10-20 min, during which time laparotomy was performed and six consecutive loops (each of 5 cm length) of the jejunum were prepared. A 3% solution of the azo dye, Evans blue (EB; MW 960.83) in phosphate-buffered saline, was instilled into each loop at a volume of 0.3 ml, this compound serving as a marker for tight junctional permeability. Thereafter, the abdomen was closed and the rats were allowed to wake up, but were killed after 60 min. The loops were dissected, opened, and rinsed with acetylcysteine in order to remove the adherent mucus layer. Each loop was weighed and incubated with formamide for 24 hr to elute the amount of EB absorbed, which was quantitated spectrophotometrically. In the control situation, the uptake was homogenous along the loops. beta-Adrenoceptor-blocking, or -stimulating agents could influence the uptake considerably. The data obtained could indicate that noradrenergic nerves, via an activation of beta 2-adrenoceptors, may cause an increase of tight junction permeability for macromolecules, but circulatory mechanisms also must be taken into account in order to explain the observed effects.