DURING synaptic transmission in the nervous system, synaptic vesicles fuse with the plasma membrane of presynaptic terminals, releasing neurotransmitter by exocytosis(1,2). The vesicle membrane is then retrieved by endocytosis and recycled into new transmitter-containing vesicles. Exocytosis in synaptic terminals is calcium-dependent(7-9), and we now report that endocytosis also is regulated by the intracellular calcium concentration ([Ca2+](i)). Capacitance measurements(10,11) in synaptic terminals of retinal bipolar neurons revealed that endocytosis was strongly inhibited by elevated [Ca2+](i) in the range achieved by Ca2+-current activation. The rate of membrane retrieval was steeply dependent on [Ca2+](i), with a Hill coefficient of 4 and half-inhibition at similar to 500 nM. At [Ca2+](i) greater than or equal to 900 nM, endocytosis was entirely absent. The action of internal calcium on endocytosis represents a novel negative-feedback mechanism controlling the rate of membrane recovery in synaptic terminals after neurotransmitter secretion. As membrane retrieval is the first step in vesicle recycling, this mechanism may contribute to activity-dependent synaptic depression.