A change in pH can alter the intracellular concentration of electrolytes such as intracellular Ca²⁺ and Na⁺ ([Na⁺]_i) that are important for the cardiac function.For the determination of the role of pH in the cardiac magnesium homeostasis, the intracellular Mg ²⁺ concentration ([Mg ²⁺]_i), membrane potential and contraction in the papillary muscle of guinea pigs using ion-selective electrodes changing extracellular pH ([pH]_o)or intracellular pH ([pH ]_i )were measured in this study. A high CO₂-induced low [pH]_o causes a significant increase in the [Mg²⁺]_i and [Na⁺]_i , which was accompanied by a decrease in the membrane potential and twitch force.The high [pH _o had the opposite effect.These effects were reversible in both the beating and quiescent muscles.The low [pH]_o-induced increase in [Mg²⁺]_i occurred in the absence of [Mg²⁺]_o .The[Mg²⁺]_i was increased by the low [pH ]_i induced by propionate.The [Mg²⁺]_i was increased by the low [pH ]_i induced by NH₄ Cl-prepulse and decreased by the recovery of [pH ]_i induced by the removal of NH₄Cl.These results suggest that the pH can modulate [Mg²⁺]_i with a reverse relationship in heart, probably by affecting the intracellular Mg²⁺ homeostasis, but not by Mg²⁺ transport across the sarcolemma.