This review summarizes the main cellular mechanisms involved in potassium regulation in plasma and skeletal muscle during exercise. The effects of exercise-induced hyperkalemia and post-exercise hypokalemia on the cardiac action potential are reviewed in light of recent research on Na+ and K+ channel activity. Specific consideration is given to K+ release from contracting skeletal muscle, K+ uptake by contracting skeletal muscle, K+ uptake by non-contracting tissues during the period of exercise, and K+ uptake by skeletal muscle recovering from contractile activity. The onset of exercise is associated with a net release of K+ from contracting skeletal muscle that results in an increase in plasma [K+]. Resultant decreases in intracellular [K+] and increases in interstitial [K+] in contracting skeletal muscle have been implicated in the fatigue process. The rate and magnitude of increase in plasma [K+] is dependent on exercise intensity, trained state of the individual, and on drugs such as beta-adrenoceptor blockers and caffeine. During exercise, the uptake of K+ from the blood by non-contracting tissues may be important in preventing plasma [K+] from rising to excessive levels that will impair skeletal muscle and myocardial excitability and contractility. Cessation of exercise results in a rapid decrease in plasma [K+], often to 3 mEq/l or less with intense exercise, that may be maintained for prolonged periods. The rapid increases and decreases in plasma [K+] with onset and cessation of exercise, respectively, has been implicated in altered myocardial function and sudden cardiac death. Recent studies suggest that increases in catecholamines during exercise are cardioprotective to the arrhythmogenic effects of hyperkalemia.