Light-dependent release of dopamine (DA) in the retina is an important component of light-adaptation mechanisms. Melanopsin-containing inner retinal photoreceptors have been shown to make physical contacts with DA amacrine cells, and have been implicated in the regulation of the local retinal environment in both physiological and anatomical studies. Here we determined whether they contribute to photic regulation of DA in the retina as assayed by the ratio of DA with its primary metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), and by c-fos induction in tyrosine hydroxylase (TH)-labelled DA amacrine cells. Light treatment (approximately 0.7 log W/m(2) for 90 min) resulted in a substantial increase in DA release (as revealed by an increase in the DOPAC : DA ratio), as well as widespread induction of nuclear c-fos in DA amacrine cells in wild-type mice and in mice lacking melanopsin (Opn4(-/-)). Light-induced DA release was also retained in mice lacking rod phototransduction (Gnat1(-/-)), although the magnitude of this response was substantially reduced compared with wild-types, as was the incidence of light-dependent nuclear c-fos in DAergic amacrines. By contrast, the DAergic system of mice lacking both rods and cones (rd/rd cl) showed no detectable light response. Our data suggest that light regulation of DA, a pivotal retinal neuromodulator, originates primarily with rods and cones, and that melanopsin is neither necessary nor sufficient for this photoresponse.