Miniature endplate currents, endplate current fluctuations ("membrane noise"), and voltage-jump current relaxations were studied in voltage-clamped frog muscle fibers during decamethonium action. All three types of experiments revealed two kinetic processes controlling the opening of endplate channels, one that reflects agonist action and another that reflects local anesthetic-like blocking activity. The kinetic constants for these two steps were evaluated from measurements of the fast and slow time constants as a function of decamethonium concentration. At -130 mV membrane potential and 130, the mean open time of decamethonium-activated channels is 2.8 msec. The forward and backward rate constants for channel blocking are -1.7 X 107 M l sec. and 103 sec-1. ITe voltage dependencies of the channel lifetime and of the blocking equilibrium are similar to those seen with pure agonists and local anesthetics, respectively. The transmitter at the nerve-muscle synapse of vertebrate skeletal muscle, acetylcholine (AcCho), acts by combining with postjunctional receptors and inducing the opening of discrete ion channels (1-3).A number of other quaternary ammonium compounds mimic this action of acetylcholine, although for some of them the maximum effect is quite feeble. Compounds that produce only small maximum potential or conductance changes are termed partial agonists. It has been generally supposed that these agonists are partial because they are relatively ineffective in triggering the conformational change of the receptor necessary for channel opening, either because the rate constants for this conformational change are such that the resting state is favored (4)