The action of beta-bungarotoxin (beta-BuTX) on spontaneous transmitter release, as monitored by miniature endplate potential (MEPP) frequency, and nerve-stimulated release, which relates directly to endplate potential (EPP) amplitude, was studied at frog sciatic nerve-sartorius muscle junctions. Three phases were found for both spontaneous and evoked release: a transient decrease followed by an increase and a later decrease leading to complete failure. The initial inhibitory phase for both spontaneous and neurally-evoked release occurred at the same time and was independent of stimulation frequency. Both the excitatory and late inhibitory phases for both types of release had a more rapid onset when stimulation frequency was increased, with the effects on evoked release occurring more rapidly than the effects on spontaneous release. Even though EPP amplitude decreased to low levels while MEPP frequency was still high, EPPs did not completely fail until the MEPPs had also declined to very low levels. In elevated K+ solutions, the number of quanta released after toxin application was only about half that released during the control experiment. During the terminal part of the late inhibitory phase of beta-BuTX action on MEPP frequency, no effect or only small transient increases were observed after La3+ administration, elevated [K+]0, or increased osmotic pressure. The present study suggests that depolarization of nerve terminals by the toxin is responsible for initiation of the excitatory phases of both types of release followed by inhibition of nerve-evoked release, and then depletion of vesicular transmitter accounts for the eventual disappearance of both MEPPs and EPPs.