Ultrastructural localization of immunoreactive corticotropin-releasing factor (CRF) was visualized for the first time in the human hypothalamus and pituitary gland with specific antibodies against human/rat CRF. In the hypothalamus most of the positive immunoreactivity to CRF was present in granules with a wide range of diameters, 50–250 nm, in the perikarya of parvocellular neurons in the paraventricular nucleus. Among these, neurosecretory type granules, 100–150 nm in diameter, were dominant, and small vesicles, 50–80 nm in diameter, were sparse. Some of surfaces of rough endoplasmic reticulum and polyribosomes were also positive in some of these cells. CRF-positive reactions were also observed in the nerve fibers of the pituitary stalk and the posterior pituitary gland revealing two types of granules: small vesicles, 50–80 nm in diameter, and neurosecretory granules, 100–150 nm in diameter. These results support the theory that the human CRF, which is identical to rat CRF, is synthesized in parvocellular neurons of paraventricular nucleus, transported in nerve fibers, and controls ACTH secretion in the human anterior lobe of pituitary gland via the port