(-)-Ephedrine has been used in the treatment of patients with myasthenia gravis. To investigate the possible effects of ephedrine on neuromuscular transmission, canine intercostal muscle endplates were studied by microelectrode techniques. At concentrations less than 10(-4) M, ephedrine had no effect on neuromuscular transmission. At a concentration of 10(-4) M, ephedrine increased the quantal content of the endplate potential by 21%. The presynaptic store of acetylcholine quanta available for immediate release was unchanged, but the probability of quantal release was increased by 16%. At this concentration, ephedrine decreased the amplitude of the miniature endplate potential by 38%. In the presence of 10(-3) M ephedrine, the miniature endplate potentials and currents became undetectable. The kinetic properties of the acetylcholine receptor channel were studied by analysis of acetylcholine-induced endplate current noise. At 10(-4) M, ephedrine reduced the channel conductance by 43% but had no effect on the open time. At 5 x 10(-4) M, ephedrine reduced the channel conductance by 84% and increased the open time by 23 percent.