The spontaneous quantal release of neurotransmitter and the fine structure of a glutamatergic synapse has been examined in the presence of ionophore X-537A. Bath applications of X-537A to extensor tibiae nerve-muscle preparations of locust, Schistocerca gregaria, increased the frequency of miniature excitatory post-synaptic potentials (min. e.p.s.p.'s). This action was completely reversible, if preparations were exposed to ionophore for less than 60 min. Application of ionophore for longer times, i.e., longer than 60 min., transiently elevated min. e.p.s.p. frequency to greater than 100/s. Following this period of high activity, miniature frequency declined to 0.4/s and were mostly of "giant" miniature potentials type. The frequency and amplitude of these "giant" miniature potentials remained unchanged after subsequent washing with standard saline. Exposure of nerve terminals to ionophore for 60 min. produced no ultrastructure changes. Longer ionophore treatments, however, led to depletion of synaptic vesicles, damaged mitochondria and disintegration of microtubules and neurofilaments within nerve terminals, suggesting irreversible changes at the locust neuromuscular junction.