The effect of changes in extracellular and intracellular magnesium content on desensitization rate in frog (Rana pipiens) sartorius muscle was studied using measurements of input conductance of single fibers during local superperfusion of the postjunctional region with carbamylcholine chloride (0.27-2.7 mM). Two intracellular KCl-filled glass capillary microelectrodes were used for current injection and recording in fibers equilibrated in high-K+ media (33-165 mM). In low-ionic strength solutions (33 mM K), time to half-decline of conductance during desensitization to carbamylcholine (T1/2) was decreased by increasing extracellular Mg2+ concentration throughout range 0-100 mM. Equivalent effects on T1/2 were produced by increased extracellular Ca2+ in lower concentrations (0-10 mM). Increase in K+ concentration or decrease of carbamylcholine concentration resulted in increased T1/2 in both Mg2+ and Ca2+ media. Increase of intracellular Mg2+ by soaking in high-Mg2+ solutions (100 mM) or by intracellular iontophoresis caused decrease in T1/2. It is concluded that Mg2+, when introduced either in the extracellular or intracellular phase, can promote increased desensitization rate and that this action is similar to but weaker than that of calcium.