1. The effects of a hypertonic bathing medium, containing either NaCl or melezitose, on the average number (m) and the time course of quantal release following an action potential were studied using focal extracellular recording methods at synaptic sites on the opener muscle of the crayfish leg.2. After the application of hypertonic saline, the rate of spontaneous quantal release increased but m decreased to a new level within 1 min; the extent of depression depended on the magnitude of the increase in tonicity until the osmolarity was 50% greater than the normal value of 0.43 osmol/l (Osm), but greater increases in tonicity exerted little further effect.3. The synaptic delays were increased and distributed over a longer range of time in hypertonic solutions; also, the latency between the first and second quantal releases in a multiple response to a single nerve impulse was also increased.4. Hypertonicity had no significant effect on the conduction velocity of the action potential, the independence of successive quantal releases in the same response, or the uniformity of the rise and fall of the probability of quanta release following an action potential, alpha(t).5. The time course of alpha(t) is prolonged in hypertonic solutions; this was manifested as an increase in the time constant of the exponential decline in alpha(t) from its peak value following the nerve impulse.5. When the potentiating agent 5-hydroxytryptamine (5-HT) was added to the hypertonic saline, m was increased, and the time course of alpha(t) was prolonged further than in the hypertonic solution alone; 5-HT produced no change in the time course of alpha(t) when it was added to normal saline, although m was increased.6. It is concluded that in this preparation hypertonicity decreases the rate of release of each quantum from the nerve terminal following a nerve impulse.