Animal experimental studies have shown that the retinohypothalamic tract (RHT) is an anatomical and functionally distinct retinofugal pathway mediating photic entrainment of circadian rhythms. In the present study, RHT projections were studied in the human brain by our recently developed postmortem tracing technique with neurobiotin as a tracer. Similar patterns of labeling were observed in brains of one control subject without neurological or mental disorders and five patients with Alzheimer's disease. The topography of RHT projections has several characteristics. (1) RHT fibers leave the optic chiasm and enter the hypothalamus medially and laterally at the anterior level of the suprachiasmatic nucleus (SCN). (2) The medial fibers enter the ventral part of the SCN and innervate the ventral SCN over its entire length, but the density decreases gradually from anterior to posterior. Labeled RHT fibers in the SCN make contact mainly with immunocytochemically positive neurotensin or vasoactive intestinal polypeptide neurons and only occasionally with vasopressin-positive neurons located in the ventral part of the SCN. (3) Only few projections to the dorsal part of the SCN and the anteroventral part of the hypothalamus were found. (4) Lateral projections reach the ventral part of the ventromedial SON and the area lateral to the SCN. No projections were observed to other hypothalamic areas. The presence of an RHT in humans suggests that the RHT may serve a function in humans similar to that demonstrated in animals.