The hypothesis that melatonin regulates circadian rod outer segment disc shedding in mammals was tested by determining the effect of exogenous melatonin on histological phagosome counts. Melatonin was administered as a subcutaneous implant or injection to photoentrained albino rats. Retinas of treated rats and paired controls were obtained at various times including the time of expected disc shedding. Phagosome counts on electron micrographs were converted to size-frequency distributions. Injected melatonin did not induce abnormal circadian shedding. However, implanted melatonin increased the frequency of large phagosomes (P < 0.01). These data further implicate melatonin in the control of disc shedding.