RAPID calcium-dependent exocytosis underlies neurotransmitter release from nerve terminals. Despite the fundamental importance of this process, neither the relationship between presynaptic intracellular calcium ion concentration ([Ca2+](i)) and rate of exocytosis, nor the maximal rate of secretion is known quantitatively. To provide this information, we have used flash photolysis of caged Ca2+ to elevate [Ca2+](i) rapidly and uniformly in synaptic terminals, while measuring membrane capacitance as ao index of exocytosis and monitoring [Ca2+](i) with a Ca2+-indicator dye. When [Ca2+](i) was abruptly increased to > 10 mu M, capacitance rose at a rate that increased steeply with [Ca2+](i). The steepness suggested that at least four calcium ions must bind to activate synaptic vesicle fusion. Half-saturation was at 194 mu M, and the maximal rate constant was 2,000-3,000 s(-1). A given synaptic vesicle can exocytose with high probability within a few hundred microseconds, if [Ca2+](i) rises above 100 mu M These properties provide for the extremely rapid signalling required for neuronal communication.