SUMMARY1. The contraction and relaxation of rings of rat thoracic aorta and bovine tail artery were examined as a function of changes in the Na+ electrochemical gradient in order to determine the role of Na-Ca exchange in the control of contractility.2. Inhibition of the Na+ pump in rat aorta by K+-free media or a low concentration (5 x 10-5M) of strophanthidin reversibly increased the contractile responses to caffeine and noradrenaline. These effects were dependent upon external Ca2+ and were observed even in the presence of a Ca2+ channel blocker (10 /LM-verapamil or 10 ,tMdiltiazem) and an ac-receptor blocker (10 /SM-phentolamine).3. Reduction of external Na+ concentration, [Na+]. (replaced by N-methylglucamine, tetramethylammonium or Tris), also caused an external Ca2+-dependent increase in tonic tension and, in rat aorta, an increase in the response to caffeine. These effects were also observed in the presence of verapamil and phentolamine. [Na+]o to 1P2 or 7-5 mm slowed the relaxation of rat aorta (5 mM-caffeine present) 3-to 5-fold, and the relaxation of bovine tail artery (without caffeine) 5-to 10-fold. These effects were seen in the presence ofverapamil and phentolamine.6. These observations are all consistent with an Na-Ca exchange transport system that can move Ca2+ either into or out of the arterial smooth muscle cells. Ca2+ entry is enhanced by raising [Na+]i (by Na+ pump inhibition) and/or lowering [Na+]0.Ca2+ extrusion from the contracted muscles is largely dependent upon external Na+. The latter observation implies that, when [Ca2+] exceeds the contraction threshold, Ca2+ efflux is mediated primarily by the Na-Ca exchanger, rather than by the sarcolemmal ATP-driven Ca2+ pump.7. When bovine tail artery was treated with verapamil and phentolamine, and t Permanent address: