The distribution and characterization of immunoreactive corticotropin-releasing factor (I-CRF) in human tissues were examined using a rat CRF RIA, immunoaffinity chromatography, gel filtration chromatography, and high performance liquid chromatography. High concentrations of I-CRF were found in the hypothalamus and pituitary stalk. In addition, I-CRF was found in the posterior pituitary, thalamus, cerebral cortex, cerebellum, pons, medulla oblongata, spinal cord, and outside the brain and in the adrenal, lung, liver, stomach, duodenum, and pancreas. The major component of I-CRF from these tissues eluted in the position of rat CRF on gel filtration chromatography. High performance liquid chromatography of this major component showed two main peaks which eluted in the positions of CRF and oxidized CRF. These elution positions were the same in all tissues. These results indicate the presence of I-CRF outside the brain and suggest that this CRF is identical to hypothalamic CRF.