We used the perforated-patch technique to examine the relationship between Ca2+ entry and exocytosis of large dense-cored vesicles in bovine adrenal chromaffin cells. Exocytosis evoked by single-step depolarizations was monitored by capacitance detection. Ca2+ entry was varied by changing external calcium concentration, stepping to different test potentials, depolarizing for different durations, or applying blockers of specific calcium channel subtypes. Regardless of protocol, the amount of exocytosis was strictly related to the integral of the voltage-clamped calcium current, raised to a power of approximately 1.5. Thus, despite the complexities of transient and nonuniform changes in submembrane calcium concentration produced by voltage-gated calcium entry, the calcium dependence of large dense- cored vesicle fusion under conditions of minimal stimulation is well approximated by a simple transfer function of summed calcium entry.