Melatonin is involved in a variety of physiological functions through activating specific receptors coupled to GTP-binding protein.Melatonin and its receptors are abundant in the retina. Here we showfor the first time that melatoninmodulates glutamatergic synaptic transmission fromcones to horizontal cells (HCs) in carp retina. Immunocytochemical data revealed the expression of the MT1 receptoroncarpHCs.Whole-cell recordings further showedthat melatonin ofphysiological concentrationspotentiatedglutamate-inducedcurrents fromisolatedcone-drivenHCs(H1cells) in a dose-dependent manner, by increasing the efficacy and apparent affinity of the glutamate receptor. The effects of melatonin were reversed by luzindole, but not by K 185, indicating the involvement of the MT1 receptor. Like melatonin, methylene blue (MB), a guanylate cyclase inhibitor, also potentiated the glutamate currents, but internal infusion of cGMP suppressed them. The effects of melatonin were not observed in cGMP-filled and MB-incubated HCs. These results suggest that the melatonin effects may be mediated by decreasing the intracellular concentration of cGMP. Consistent with these observations, melatonin depolarized the membrane potential of H1 cells and reduced their light responses, which could also be blocked by luzindole. These effects of melatonin persisted in the presence of the antagonists of receptors for dopamine, GABA and glycine, indicating a direct action of melatonin on H1 cells. Such modulation by melatonin of glutamatergic transmission from cones to HCs is thought to be in part responsible for circadian changes in light responsiveness of cone HCs in teleost retina.