Ca(2+)-activated Cl(-) currents (I(Cl,Ca)) were examined using fluorescence confocal microscopy to monitor intracellular Ca(2+) liberation evoked by flash photolysis of caged inositol 1,4, 5-trisphosphate (InsP(3)) in voltage-clamped Xenopus oocytes. Currents at +40 mV exhibited a steep dependence on InsP(3) concentration ([InsP(3)]), whereas currents at -140 mV exhibited a higher threshold and more graded relationship with [InsP(3)]. Ca(2+) levels required to half-maximally activate I(Cl,Ca) were about 50% larger at -140 mV than at +40 mV, and currents evoked by small Ca(2+) elevations were reduced >25-fold. The half-decay time of Ca(2+) signals shortened at increasingly positive potentials, whereas the decay of I(Cl,Ca) lengthened. The steady-state current-voltage (I-V) relationship for I(Cl,Ca) exhibited outward rectification with weak photolysis flashes but became more linear with stronger stimuli. Instantaneous I-V relationships were linear with both strong and weak stimuli. Current relaxations following voltage steps during activation of I(Cl,Ca) decayed with half-times that shortened from about 100 ms at +10 mV to 20 ms at -160 mV. We conclude that InsP(3)-mediated Ca(2+) liberation activates a single population of Cl(-) channels, which exhibit voltage-dependent Ca(2+) activation and voltage-independent instantaneous conductance.