The administration of selective ₁ (phenylephrine)-,  (isoproterenol)-, or mixed (epinephrine) adrenergic agonists induces a marked Mg²⁺ extrusion from perfused rat livers. In the absence of extracellular Ca²⁺, phenylephrine does not induce a detectable Mg²⁺ extrusion, isoproterenol-induced Mg²⁺ mobilization is unaffected, and epinephrine induces a net Mg²⁺ extrusion that is lower than in the presence of extracellular Ca²⁺ and quantitatively similar to that elicited by isoproterenol. In the absence of extracellular Na⁺, no Mg²⁺ is extruded from the liver irrespective of the agonist used. Similar results are observed in perfused livers stimulated by glucagon or 8-chloroadenosine 3',5'-cyclic monophosphate. In the absence of extracellular Na⁺ or Ca²⁺, adrenergic-induced glucose extrusion from the liver is also markedly decreased. Together, these results indicate that liver cells extrude Mg²⁺ primarily via a Na⁺-dependent mechanism. This extrusion pathway can be activated by the increase in cellular cAMP that follows the stimulation by glucagon or a specific -adrenergic receptor agonist or, alternatively, by the changes in cellular Ca²⁺ induced by the stimulation of the ₁-adrenoceptor. In addition, the stimulation of the ₁-adrenoceptor appears to activate an auxiliary Ca²⁺-dependent Mg²⁺ extrusion pathway. Finally, our data suggest that experimental conditions that affect Mg²⁺ mobilization also interfere with glucose extrusion from liver cells.