Alkalosis enhances human exercise performance and in contracting rat muscle, reduced K⁺ loss. We investigated alkalosis effects on K⁺ regulation, ionic regulation and fatigue during intense exercise in nine untrained volunteers. Concentric finger flexions were conducted at 75% peak workrate (~3 W) until fatigue, under alkalosis (ALK, NaHCO₃, 0.3g.kg^-1) and control (CON, CaCO₃) conditions, 1 month apart in a randomised, double-blind, crossover design. Deep antecubital venous (v) and radial arterial (a) blood was drawn at rest, during exercise and recovery, to determine arteriovenous differences for electrolytes, fluid shifts, acid-base and gas exchange. Finger flexion exercise barely perturbed arterial plasma ions and acid-base status, but induced marked arterio-venous changes. ALK elevated [HCO₃^-] and PCO₂, and lowered [H⁺] (P<0.05). Time to fatigue increased substantially during ALK (25±8%, P<0.05), whilst both [K⁺]_a and [K⁺]_v were reduced (P<0.01) and [K⁺]_a-v during exercise tended to be greater (P=0.056, n=8). Muscle K⁺ efflux at fatigue was greater in ALK (21.2±7.6 ìmol.min-1, 32±7%, P<0.05, n=6), but peak K⁺ uptake rate was elevated during recovery (15±7%, P<0.05) suggesting increased muscle Na⁺,K⁺-ATPase activity. ALK induced greater [Na⁺]_a, [Cl^-]_v, muscle Cl^- influx and muscle [Lac^-] efflux during exercise and recovery (P<0.05). The lower circulating [K⁺] and greater muscle K⁺ uptake, Na⁺ delivery and Cl^- uptake with ALK, are all consistent with preservation of membrane excitability during exercise. This suggests that lesser exercise-induced membrane depolarisation may be an important mechanism underlying enhanced exercise performance with ALK. Hence ALK was associated with improved regulation of K⁺, Na⁺, Cl^- and Lac^-.