We explored the hypothesis that postaglandin-induced vasodilation is caused by activa- tion of the electrogenic sodium-potassium pump which results in membrane hyperpolarization and relaxation of vascular smooth muscle. Helical strips of rat tail artery relax in response to potassium after norepinephrine-induced contractions in physiological salt solution containing a low-potassium concentration. The amplitude of this potassium-induced relaxation is used as an index of sodium- potassium ATPase activity. It was observed that PGAi, PGE2, and PGF2o(10∼6g/ml) significantly enhanced the magnitude of potassium-induced relaxation. PGA2and PGEi (10∼6g/ml) had no significant effect. PGE2caused relaxation of contractions induced by either 25 mM KC1 or norepinephrine (10∼9g/ ml), and these relaxations were inhibited by 10∼4M ouabain. Indomethacin (5.3 × 10"" g/ml) and meclofenamate (10∼6g/ml) reduced the magnitude of potassium-induced relaxation by more than 30% of control. PGF2a(10∼sg/ml) reversed the inhibition of potassium relaxation by meclofenamate. These observations suggest that prostaglandins induce vascular smooth muscle relaxation by stimulation of the sodium pump and that endogenous prostaglandins normally potentiate potassium relaxation. Circ Res 46: 714-720, 1980