Ring segments of the rabbit ear artery were studied in the normal configuration (where drugs entered the media mainly through the adventitia) and in the everted configuration (where drugs entered mainly through the intima). Norepinephrine (NE) produced a faster response when added to the intima. This difference was not due to NE uptake mechanisms or asymmetry of different types of alpha-receptor. However, tetraethylammonium chloride (which abolishes rectification and increases membrane electrical activity) selectively increased the velocity of contraction of the normal artery segments to NE. These results suggest that approximately 50% of the difference between the intimal and adventitial velocity of contraction to NE is due to the presence of an intimal electromechanical coupling mechanism which does not operate at the adventitia. The remaining difference may be due to a closer proximity of medial alpha-receptor to the intimal surface.