A circadian rhythm of dopamine metabolism can be induced by daily injections of melatonin, and recent findings suggest that melatonin in the mouse retina may contribute to circadian rhythms of protein phosphorylation in photoreceptors. The fact that a band around 80 kDa was detected in the retinal extract of WT mice is intriguing and deserves some discussion. Previous studies have reported that melatonin receptors have the potential to form heteromeric complexes and these receptors were indeed among the first G protein-coupled receptors that have been shown to homo- and heteromerize in a constitutive manner when transfected in HEK 293 cell at physiological levels. Therefore, it is possible that the band observed at 80 kDa may represent the MT1 receptor in the homodimeric or heteromeric form. Therefore it is also possible that this band may be the result of non-specific binding of the MT1 receptor antibody. Additional studies will be required to resolve this important issue. The data obtained with immunocytochemistry are also consistent with previously published data using in situ hybridization in the mouse or with ICCH in rat and human, which showed that MT1 receptors are widely distributed within the retina. Our study expands on these previous reports by showing that MT1 receptors are located on the rod, and possibly the cone photoreceptors. The fact that MT1 receptors are present on the photoreceptors further supports our previous study where we reported that MT1 signaling is an important modulator of photoreceptor functions and viability. Previous studies have also shown that melatonin is synthesized in the photoreceptors, and its synthesis is directly controlled by the circadian clock. The fact that MT1 receptors are expressed on the cells responsible for its synthesis suggests that melatonin plays an autocrine role within the photoreceptors, and on the circadian clock located in these cells. A previously published study reported that ipRGCs express dopamine receptors, and our new data expand this previous finding by demonstrating that MT1 receptors are also present on the ipRGCs. Such a result would suggest that the melatonin-dopamine feedback loop which regulates the rods and cones circadian physiology may be also involved in the modulation of circadian rhythms in the ipRGCs. Our previous study had shown that melatonin via MT1 actually controls the rhythms of the scotopic and photopic ERGs in C3H mice, when the mice are kept in a 12 h light: 12 h dark cycle, and other investigations performed with melatonin-deficient mice have shown that the amplitude of the scotopic ERGs is not rhythmic in mice housed in constant conditions, and thus demonstrating that the scotopic ERGs are not under circadian control. Since melatonin is believed to be a key regulator of circadian functions within the retina, we decided to investigate whether the scotopic ERG was under circadian regulation in a melatonin-proficient mouse. On the other hand, a circadian rhythm in the photopic ERGs was observed in WT mice, and was also observed in melatonindeficient mice suggesting that melatonin may not be directly involved in the regulation of the photopic ERGs. Although these results may appear surprising, they are not completely unexpected since circadian regulation of DA and DOPAC is abolished in melatonindeficient mice, and therefore it is unlikely that the circadian regulation of the photopic ERGs in melatonin-deficient mice is driven by the circadian regulation of the retinal dopaminergic system. A previous investigation has shown that removal of melanopsin may affect the circadian regulation of the photic ERG.