The regional distribution of pro-opiocortin-derived peptides and methionine enkephalin was investigated in human brain post-mortem. Sequence-directed radioimmunoassays for β-endorphin, γ-lipotropin, adrenocorticotrophin, corticotrophin-like intermediate lobe peptide (ACTH18–39, CLIP) α-MSH and methionine enkephalin were used and 40 different human brain areas were assayed. The regional distribution of all the pro-opiomelanocortin-derived immunoreactivi-ties were correlated with highest amounts of β-endorphin, γ-lipotropin and ACTH in the hypothalamus, amygdala, peri-ventricular grey, substantia nigra and superior colliculus. The distribution of β-endorphin, γ-lipotropin and ACTH did not parallel the distribution of methionine-enkephalin immunoreactivity which was present in the globus pallidus, nucleus accumbens and substantia nigra. Gel exclusion chromatography (G-50) showed that pro-opiocortin-related peptides in the human hypothalamus and periventricular grey separated in positions consistent with the major immunoreactive forms being β-endorphin, γ-lipotropin, ACTH and CLIP.