In this paper we report our observations of the relationship of paired-pulse facilitation (PPF) with synaptic release or release failure at small numbers of synaptic sites. Minimal stimulation protocols were employed to enable the activation of only one or a few axons which synapse onto CA1 pyramidal cells in the hippocampus. Excitatory postsynaptic currents (EPSCs) in response to paired stimulation were measured. On the analysis of the data, we examined the effects of failure and synaptic release on PPF, and found that PPF was observed as a decrease in failures of synaptic release in response to test stimuli which were preceded by conditioning stimuli that evoked synaptic release. The test-pulse failure rate following conditioning pulse failures was indistinguishable from the overall conditioning pulse failure rate. It is postulated that the mechanism of paired-pulse facilitation is presynaptic and associated with successful synaptic release in response to the conditioning stimulus.