Photoreceptor light responses are encoded by changes in synaptic vesicle release. Release from rods is triggered by the opening of calcium channels beneath plate-like synaptic ribbons. Maintained depolarization can activate CICR and enhance release. Using total internal reflection fluorescence microscopy (TIRFM) to visualize release of single synaptic vesicles, we tested whether CICR enhances release from rods by stimulating fusion at non-ribbon sites.Rods from salamander retina were loaded with activity-dependent dyes, FM1-43 or dextran-conjugated pHrodo, and visualized by TIRFM. Rods were depolarized with steps to −10 mV under voltage-clamp or by puff application of 50 mM KCl. CICR was activated with 10 μM ryanodine and inhibited with 100 μM ryanodine. Ribbon locations were identified with a fluorescent ribbon-binding peptide or from hot spots of depolarization-evoked calcium entry visualized with Fluo5F.In terminals loaded with FM1-43 or pHrodo, depolarization stimulated rapid disappearance of vesicles with kinetics similar to that measured electrophysiologically. Additionally, stimulation-evoked vesicle disappearance was blocked by Cd2+, indicating that it was due to calcium-dependent exocytosis. Vesicles docked for about 200 ms before fusion. Most release events occurred close to ribbons, but some also occurred further away. Activation of CICR with 10 μM ryanodine stimulated intracellular calcium increases and vesicle release. Ryanodine-evoked release events were less clustered than release evoked by depolarization, consistent with greater non-ribbon release. The spread of calcium evoked by 500 ms steps (but not 50 ms steps) was inhibited by blocking CICR with 100 μM ryanodine in the patch pipette. Release evoked by 500 ms steps also involved sites further from the ribbon than release evoked by 50 ms steps. These results indicate that the stimulation of CICR by maintained depolarization enhances release from rods by triggering fusion of vesicles at non-ribbon sites.