Using high resolution capacitance (Cm) measurement techniques, we mapped the kinetics of exocytosis evoked by brief (5-100 ms) depolarizations that activate voltage-dependent Ca2+ channels in rat adrenal chromaffin cells. After correcting the Cm signal for contributions from Na+ channel-gating charge movements, the initial kinetics of exocytosis were consistent with depolarization-triggered release occurring initially from an immediately releasable pool of only approximately 17 secretory vesicles. In contrast, repetitive application of longer depolarizations evoked release from a distinct, larger readily releasable pool of approximately 170 vesicles. Our results suggest that the secretory response of a chromaffin cell to an action potential is limited by the size of the immediately releasable pool rather than by a fusion mechanism that is slower than that at synapses.