We investigated modulatory role of cytoplasmic chloride ion concentration ([Cl^-]_i) on secretory activity in mouse adrenal slices. Slow photo-release of caged Ca²⁺ (NP-EGTA) was used to activate Ca²⁺ -dependent exocytosis, measured as membrane capacitance changes (C_m) using whole-cell patch-clamp technique. Slow, ramp-like changes in intracellular free Ca²⁺ concentration ([Ca²⁺]_i, Fura-6F photometry) enabled high temporal resolution and more precise determination of Ca²⁺ dependency of the elicited exocytotic bursts. Intracellular clamp to high [Cl^-]_i (155 mM) resulted in a significant change in the amplitude as well as maximal rate of C_m change, however Ca²⁺-sensitivity of the exocytotic process has not been affected. At 155 mM [Cl^-]_i, the amplitude of the secretory bursts were approximately two-times larger compared to low [Cl^-]_i (14 mM). Similarly, the maximal rate of C_m change during bursts was significantly faster at high [Cl^-]_i (400 ± 44 fF/s) compared to the low [Cl^-]_i (233 ± 38 fF/s). The sensitivity of the exocytotic machinery did not depend on [Cl^-]_i as Ca²⁺ concentration required for the half maximal exocytotic activity was comparable (EC₅₀ = 0.4 mM). Taken together, the influence of [Cl^-]_i on secretory amplitude and rate but not on its sensitivity for Ca²⁺ corroborates the modulatory role of chloride ions in the promotion of vesicular maturation.