We discuss a model of presynaptic vesicle dynamics, which allows for heterogeneity in release probability among vesicles. Specifically, we explore the possibility that synaptic activity is carried by two types of vesicles; first, a readily releasable pool and, second, a reluctantly releasable pool. The pools differ regarding their probability of release and time scales on which released vesicles are replaced by new ones. Vesicles of both pools increase their release probability during repetitive stimulation according to the buildup of Ca(2+) concentration in the terminal. These properties are modeled to fit data from the calyx of Held, a giant synapse in the auditory pathway. We demonstrate that this arrangement of two pools of releasable vesicles can account for a variety of experimentally observed patterns of synaptic depression and facilitation at this synapse. We conclude that synaptic transmission cannot be accurately described unless heterogeneity of synaptic release probability is taken into account.