Relaxation of the rat thoracic aorta induced by sodium nitroprusside, 8-bromo-cyclic GMP and cyclic nucleotide phosphodiesterase inhibitor M & B 22,948 was inhibited by exposure to K<sup>+</sup>-free solution and ouabain in a concentration-dependent manner. Relaxation occurring with the change in potassium concentration in media from 1 to 2 to 10 mM was increased by sodium nitroprusside, 8-bromo-cyclic GMP and M & B 22,948. Thus, agents and procedures known to decrease and increase the activity of the Na<sup>+</sup>, K<sup>+</sup>-pump, and presumably alter the membrane potential, inhibited and enhanced relaxation, respectively. Exposure to 1 mM K<sup>+</sup> solution increased the relaxation to low concentrations of sodium nitroprusside, but had no effect on relaxation induced by 8-bromo-cyclic GMP or M & B 22,948. Thus, another procedure which inhibits the Na<sup>+</sup>, K<sup>+</sup>-pump enhanced the effect of low concentrations of sodium nitroprusside on relaxation. Ouabain had no effect on sodium nitroprusside-induced accumulation of cyclic GMP. These results suggest that sodium nitroprusside may induce relaxation through cyclic GMP formation, effects on the Na<sup>+</sup>, K<sup>+</sup>-pump and/or hyper-polarization of the smooth muscle cell membrane.