Melatonin, a hormone originally discovered in the pineal gland, has also been found in the retina of several vertebrate species. The enzyme system for melatonin synthesis also exists in the retina, where the activity of one such enzyme, (serotonin N-acetyltransferase) varies with changes in light intensity in a circadian pattern. As the activity of dopamine containing amacrine neurones of the retina is influenced by changes in illumination it was of interest to determine the effect of melatonin and its precursors, serotonin and N-acetylserotonin, on the release of 3H-dopamine from rabbit retina. I report here that picomolar concentrations of melatonin (IC50 9pM) selectively inhibited the calcium-dependent release of 3H-dopamine from rabbit retina, but not from striatum. Melatonin, was 1,000 times more potent than its precursor N-acetylserotonin in inhibiting the release of 3H-dopamine in retina, while the putative neurotransmitter serotonin, was inactive. It is suggested that the light-dependent production of melatonin could play a physiological role in modulating the activity of dopamine-containing neurones in the retina.