Synapses in the central nervous system can be very unreliable: stimulation of an individual synapse by an action potential often does not lead to release of neurotransmitter. The probability of transmitter release is not always the same, however, which enables the average strength of synaptic transmission to be regulated by modulation of release probability. Release probability is believed to be determined by the number of fusion competent vesicles (the readily releasable vesicle pool) and the release probability per vesicle. Studies from single synapses have shown that release probability correlates with the size of the readily releasable pool of vesicles across the population of excitatory CA3-CA1 synapses, both in hippocampal slices and in cultured cells. Here I present evidence that the same relationship exists between release probability and the size of the readily releasable vesicle pool within individual synapses, further suggesting that the size of the readily releasable pool helps determine release probability. In addition, using a simple model, I examine how both the number of readily releasable vesicles and the average release probability per vesicle change during trains of high frequency stimulation, and present evidence for non-uniformity of the release probability among vesicles. © 2002 ISDN. Published by Elsevier Science Ltd. All rights reserved.