Zinc is associated with glutamatergic pathways in brain and retina, yet its role in neuromodulation remains unknown. High concentrations of reactive zinc in vertebrate photoreceptor terminals suggest a neuromodulatory role in the outer plexiform layer but zinc release has not been demonstrated. Using the membrane-impermeable form of the Zn(2+) sensitive fluorescent dye Newport Green, we have demonstrated increased release of Zn(2+) from the rat retina in response to potassium-induced depolarization of retinal cells. This increase was greatest in the outer retina with densest bands observed in the outer plexiform layer and photoreceptor inner segment regions of rat retinal slices.