The morphological characteristics and distribution patterns of neurons immunoreactive for antisera against six biologically active peptides were examined by indirect immunofluorescence in the human brain. The peptides studied were: met-enkephalin, leu-enkephalin, substance P, somatostatin, cholecystokinin and vasoactive intestinal peptide. The tissue samples for this study were removed, dissected and placed into fixative within 4 h post-mortem. Regional differences throughout the entire neuraxis were observed in the localization of cell bodies, fibers and terminals for the various peptides. The observations reported in this article demonstrate certain distribution patterns for peptide immunoreactivities that appear to be specific to the human brain when compared to other species. These morphologic studies establish a valuable framework for the further analysis of the role of peptide-containing neuronal circuits in normal and diseased human brain.