At many synapses, vesicle depletion is thought to represent the dominant mechanism of short-term depression during high-frequency signalling. Two distinct populations of vesicles have been described with different vesicle replenishment kinetics (Sakaba and Neher, 2001), but fast vesicle replenishment has also been explained with only one population of vesicles (Saviane and Silver, 2006; Hosoi et al., 2007). In any case, sustained activity requires that vesicles are rapidly reloaded at the active zone (AZ). At tonic synapses fast vesicle replenishment has been linked to large electron-dense ribbons which support vesicle trafficking towards the membrane. However, the molecular mechanisms of this traffic remain unclear and it is also unclear whether phasic synapses use comparable mechanisms. Drosophila Bruchpilot (BRP), whose N-terminal half encodes the Drosophila CAST homologue, was shown to cluster calcium channels within the AZ and thus allow efficient transmitter release at the phasic Drosophila neuromuscular junction (Kittel et al., 2006). We found that the lack of BRP reduces release probability but the number of ready releasable vesicles is unaffected. In addition, synaptic depression was stronger during trains of stimuli, even when the extracellular calcium was elevated to "rescue" the current amplitude under resting conditions. In mutants that lack only the last 16 C-terminal amino acids of the 1740 amino acid protein Bruchpilot, the current amplitude under resting conditions was unchanged and the electron dense material appeared unaffected on an electron microscopic level. However, the number of vesicles surrounding the electron dense material was reduced and synaptic depression during sustained activity was stronger compared to control. Consistent with findings in synapsin mutants and in animals with a reduced number of calcium channels, these results indicate that the tethering of vesicles to the C-terminal domain of BRP accelerates vesicle reloading at the AZ of a phasic synapse.