Photoreceptor disc shedding and their phagocytosis by the retinal pigment epithelium undergo a daily rhythm entrained by an intrinsic oscillator involving melatonin and dopamine in non-mammals. Such a mechanism is not demonstrated in mammals, but the rhythm of photoreceptor renewal can be modulated by exogenous melatonin and dopamine. The present experiments were designed to show whether a direct action of DA occurs on pigment epithelial cells, and to identify the receptor mediating this action. Primary cultures of bovine retinal pigment epithelium were incubated with bovine rod outer segments in the presence of dopamine, D1 and D2 agonists, D1 antagonist and forskolin. Dopamine, D1 agonist and forskolin decreased phagocytosis, while D2 agonist was inactive. Thus dopamine slows pigment epithelium phagocytosis in vitro through a D1 receptor. Increased phagocytosis following blockade of the receptor by an antagonist suggests a more complex modulation of phagocytosis by dopamine.