Abstract The actions of ephedrine were studied using intracellular recording techniques in guinea pig intercostal muscle fiber. After application of ephedrine (10 −5 −10 −4 M), miniature end-plate potential (MEPP) amplitude was decreased in a concentration-dependent manner. A greater depression in amplitude of end-plate potentials (EPP) was observed in preparations immobilized with d-tuboeurarine. In addition, ephedrine depressed the transient depolarization produced by iontophoretically applied acetylcholine (ACh). In normal Krebs solution and high Mg 2+ solution, 10 −4 M ephedrine increased MEPP frequency but did not alter the quantal content of EPPs in high Mg 2+ blocked muscle. In these preparations, EPP amplitude did not change significantly. These results suggested that in the absence of a postsynaptic receptor blocking agent, a slight presynaptic action of ephedrine may offset the decreased responsiveness of the postsynaptic membrane. In addition, no significant alterations of resting membrane potential or the electrical characteristics of the membrane were recorded. Pretreatment of a mouse phrenic nerve-diaphragm preparation with ephedrine did not protect against the irreversible blockade by α-bungarotoxin. These results suggested that ephedrine may depress ACh potentials, MEPPs, and EPPs in dTc-blocked muscle by acting postsynaptically at a site on or associated with the ACh receptor other than the ACh recognition site.