Raising extracellular K⁺ concentration ([K⁺]_o) around mesenteric resistance arteries reverses depolarization and contraction to phenylephrine. As smooth muscle depolarizes and intracellular Ca²⁺ and tension increase, this effect of K⁺ is suppressed, whereas efflux of cellular K⁺ through Ca²⁺-activated K⁺ (K_Ca) channels is increased. We investigated whether K⁺ efflux through K_Ca suppresses the action of exogenous K⁺ and whether it prestimulates smooth muscle Na⁺-K⁺-ATPase. Under isometric conditions, 10.8 mM [K⁺]_o had no effect on arteries contracted >10 mN, unless 100 nM iberiotoxin (IbTX), 100 nM charybdotoxin (ChTX), and/or 50 nM apamin were present. Simultaneous measurements of membrane potential and tension showed that phenylephrine depolarized and contracted arteries to 32.2 ± 2.3 mV and 13.8 ± 1.6 mN (n = 5) after blockade of K_Ca, but 10.8 mM K⁺ reversed fully the responses (107.6 ± 8.6 and 98.8 ± 0.6%, respectively). Under isobaric conditions and preconstriction with phenylephrine, 10.7 mM [K⁺]_o reversed contraction at both 50 mmHg (77.0 ± 8.5%, n = 9) and 80 mmHg (83.7 ± 5.5%, n = 5). However, in four additional vessels at 80 mmHg, raising K⁺ failed to reverse contraction unless ChTX was present. Increases in isometric and decreases in isobaric tension with phenylephrine were augmented by either ChTX or ouabain (100 µM), whereas neither inhibitor altered tension under resting conditions. Inhibition of cellular K⁺ efflux facilitates hyperpolarization and relaxation to exogenous K⁺, possibly by indirectly reducing the background activation of Na⁺-K⁺-ATPase.