The immunocytochemical distribution of Proopiomelanocortin (POMC) peptides (β-endorphin, ACTH, α-MSH, 16K fragment) was studied in the brain of the rhesus monkey ( Macaca mulatta). Some animals were administered colchicine intracerebroventricularly prior to sacrifice to enhance the visualization of perikaryal immunoreactivity. Immunoreactive perikarya are localized to hypothalamic infundibular nucleus, giving rise to several distinct projections. Rostral projections extend through midline diencephalic and preoptic areas, and enter the telencephalon. Along this course, immunoreactive fibers are seen in midline hypothalamic and preoptic nuclei, nucleus of the diagonal band, olfactory tubercle, nucleus accumbens, bed nucleus of stria terminalis, septum, and other limbic structures in telencephalon. Caudal to the anterior commissure, some fibers ascend dorsally to enter the midline thalamus, which they innervate. Lateral projections of the infundibular perikarya course through the medial-basal hypothalamus, dorsal to the optic tracts, and enter the amygdala region where they innervate more medially situated amygdaloid nuclei. Caudal projections of the POMC neurons also extend through midline diencephalon, some coursing along a periventricular path to innervate midline hypothalamic and thalamic nuclei. This projection extends into the mesencephalic substantia grisea centralis and may also contribute to the innervation of more dorsally situated nuclei in the pons and medulla, such as the parabrachial nuclei and nucleus tractus solitarius. Other caudal projections originating in the hypothalamus course through the ventral tegmentum of mesencephalon and pons and may contribute to the innervation of midline raphe and other ventrally situated nuclei in the pons and medulla. The distribution of immunoreactive perikarya and fibers in the brain of rhesus monkey is strikingly similar to that found in the rat brain. However, subtle differences appear to exist in the innervation patterns of particular brain regions.