The distribution of pro-somatostatin-derived-peptide-positive profiles was examined by indirect immunohistofluorescence in nine post-mortem human brains (age 58-73 years). Three specific antisera were used for this study which recognize, respectively, somatostatin-28, somatostatin-28 (1-12) and somatostatin (1-14). Pro-somatostatin-derived-peptide-positive immunoreactive profiles were observed throughout the neuraxis. Cell bodies were found within archeo-, paleo- and neocortical areas, the subcortical white matter, in the nucleus accumbens, caudate nucleus and putamen, as well as in the hypothalamus, the reticular thalamic nucleus and the reticular formation of the brainstem. Fibers and terminals were seen in the same areas as well as in various thalamic nuclei, in the brainstem and spinal cord. Pro-somatostatin-derived-peptide-positive fibre tracts include the bed nucleus of the stria terminalis, the diagonal band of Broca, the stria medullaris, the inter-thalamic adhesion, the posterior commissure and the spinothalamic tract. Furthermore, differences between human and animal brains were noted and some somatostatin systems reported which may be implicated in certain human neuropathological states.