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The amplitude of miniature end-plate potentials (m.e.p.p.s), recorded at the frog neuromuscular junction in a normal ionic environment and in absence of drugs, was examined following 10-450 nerve impulses using conventional electrophysiological techniques and on-line computational analysis. In both contracting preparations and non-contracting preparations pre-treated with glycerol, 100 or more nerve impulses resulted in a maximal fall in mean amplitude of about 20% with recovery apparent over the next 10-20 min. In an altered ionic environment with a lowered Ca and raised Mg concentration, 450 nerve impulses did not produce a decrease in mean amplitude but a similar reduction was seen following a larger number of impulses. The reduction in amplitude was estimated to follow the release of the order of 5000-10000 quanta at end-plates in a normal ionic environment and on average 17000 quanta in the presence of a lowered Ca and raised Mg concentration. Changes in the mean size of the spontaneous quantal response is considered to be a presynaptic event and to reflect the loss and slow recovery of larger packets of transmitter from a vesicular store that is readily released by nerve impulses.