This study reports the identification of a novel human opsin, melanopsin, which is expressed in the inner retina of mammals. The melanopsin gene consists of 10 exons and is mapped to chromosome 10q22, differing significantly from other human opsins that typically have four to seven exons. In situ hybridization histochemistry shows that melanopsin expression is restricted to cells within the ganglion and amacrine cell layers of the primate and murine retinas, but not in the photoreceptor cells of the outer retina. The unique localization of melanopsin suggests that it may mediate nonvisual photoreceptive tasks, such as regulating circadian rhythms and suppressing pineal melatonin. The anatomical distribution of melanopsin-positive retinal cells is similar to the pattern of cells known to project from the retina to the suprachiasmatic nuclei of the hypothalamus, a primary circadian pacemaker. The study also discusses the sequence homology of melanopsin with invertebrate opsins and its potential role in mammalian circadian photoreception.This study reports the identification of a novel human opsin, melanopsin, which is expressed in the inner retina of mammals. The melanopsin gene consists of 10 exons and is mapped to chromosome 10q22, differing significantly from other human opsins that typically have four to seven exons. In situ hybridization histochemistry shows that melanopsin expression is restricted to cells within the ganglion and amacrine cell layers of the primate and murine retinas, but not in the photoreceptor cells of the outer retina. The unique localization of melanopsin suggests that it may mediate nonvisual photoreceptive tasks, such as regulating circadian rhythms and suppressing pineal melatonin. The anatomical distribution of melanopsin-positive retinal cells is similar to the pattern of cells known to project from the retina to the suprachiasmatic nuclei of the hypothalamus, a primary circadian pacemaker. The study also discusses the sequence homology of melanopsin with invertebrate opsins and its potential role in mammalian circadian photoreception.