Synaptic depression was studied using capacitance measurements in synaptic terminals of retinal bipolar neurons. Single 250 msec depolarizations evoked saturating capacitance responses averaging approximately 150 fF, whereas trains of 250 msec depolarizations produced plateau capacitance increases of approximately 300 fF. Both types of stimuli were followed by pronounced synaptic depression, which recovered with a time constant of approximately 8 sec after single pulses but required >20 sec for full recovery after pulse trains. Inactivation of presynaptic calcium current could not account for depression, which is attributed instead to depletion of releasable and reserve vesicle pools that are recruited and replenished at different rates. Recovery from depression was normal in the absence of fast endocytosis, suggesting that replenishment was from a reserve pool of preformed vesicles rather than from preferential recycling of recently fused vesicles. Given the in vivo light response of the class of bipolar neuron studied here, it is likely that, under at least some illumination conditions, the cells produce a fast and phasic bout of exocytosis rather than tonic release.