Immunohistochemical studies with antisera to somatostatin have, in many instances, led the way to our present understanding of the peptidergic nervous system. Somatostatin was among the first of the hypophysiotropic hormones shown to be contained in diverse neuronal circuits outside of the hypothalamus. For example, somatostatin is found within neurons ranging in location from the cerebral cortex to primary sensory neurons to enteric neurons within the gut wall. Somatostatin was also the first neuropeptide demonstrated to coexist within vertebrate neurons that also produce a classical neurotransmitter. Since this initial demonstration in sympathetic ganglionic neurons, somatostatin and numerous other neuropeptides have been demonstrated to coexist with a variety of classical neurotransmitters. The "rules" for coexistence are not clear, since somatostatin coexist in some instances with norepinephrine, in other cases with GABA, and probably with other classical transmitters as well. In some neurons, somatostatin also coexists with certain other neuropeptides. Finally, the specificity of immunohistochemical localizations of somatostatin has now been confirmed by virtue of the co-staining of somatostatin neurons with antisera to other portions of the biosynthetic precursor to somatostatin.