The triggering of endocytosis by exocytosis and its regulation by intracellular calcium concentration ([Ca²⁺]_i) are well-established phenomena. Here we show that the mechanism linking these two processes is dependent on microdomain-[Ca²⁺]_i similar to that which triggers exocytosis. We further show that compensatory endocytosis is eliminated by blocking proteins that mediate endocytosis (dynamin and AP2) as well as by disrupting exocytotic protein synaptobrevin/VAMP. Furthermore, these manipulations all have a limited, retrograde action on exocytosis, delaying recruitment of release-ready vesicles and enhancing short-term depression. The latter effect sets in so rapidly, that it cannot be explained by the non-availability of recycled vesicles. Rather, we postulate that perturbation of a step linking exocytosis and endocytosis temporarily prevents new vesicles from docking at specialized sites for exocytosis.