Abstract Na +-independent Mg 2+ efflux from Mg 2+-loaded human, rat and chicken erythrocytes was reduced by extracellular Cl −. Na +-independent Mg 2+ efflux at low extracellular Cl − concentration (sucrose medium) was inhibited by SITS and was nearly insensitive to SITS in 150 mM choline Cl medium. The inhibition of Mg 2+ efflux by extracellular Cl − and DIDS could be overcome by the lipophilic permeant tetraphenylphosphonium cation. Na +-independent Mg 2+ efflux from human and rat erythrocytes in sucrose and choline Cl medium was inhibited by cAMP and by amiloride and amiloride analogues. The results indicate that Na +-independent Mg 2+ efflux in high Cl − medium is performed by a similar or the same Mg 2+ efflux system, operating in sucrose medium in which the efflux of Mg 2+ is accompanied by the efflux of Cl − for charge compensation.