The tetradecapeptide somatostatin has been shown to have a widespread distribution in the rat brain. Except for its role in the inhibition of growth hormone secretion, the function of this molecule in the remainder of the central nervous system is unknown. To address this problem, the distribution of somatostatin-like immunoreactivity in the guinea-pig brainstem was examined systematically. Of 116 nuclei and/or areas, 34 nuclei had somatostatin neurons, 32 did not have any immunoreactivity and the remainder had immunoreactive fibers and/or terminals. Cranial nerve motor nuclei--somatic, branchiomeric and visceral--did not contain somatostatin neurons; somatostatin fibers were present in all nuclei with the exception of the somatic motor nuclei which innervate the ocular muscles. Of the cranial nerve sensory nuclei--both somatic and visceral--somatostatin neurons were present only in the somatic nuclei nervi spinal trigeminal caudalis, interpolaris and oralis; all of these nuclei, however, contained substantial numbers of immunoreactive fibers. Somatostatin neurons and fibers were also present in the spinal somatic sensory nuclei cuneatus medialis and gracilis. Of the cranial nerve special somatic sensory nuclei, somatostatin neurons were present in two vestibular nuclei--spinalis and medialis--and in the ventral cochlear nucleus. Not all of these nuclei contained somatostatin fibers. Of the nuclei related to the auditory system, somatostatin neurons were present only in the dorsal and ventral trapezoid nuclei and in the cortex of the inferior colliculus. In nuclei of the visual system in the brainstem, somatostatin neurons were present only in the superior colliculus. Of the raphe nuclei, four had somatostatin neurons--magnus, obscurus, pallidus and superior centralis; somatostatin fibers were present in all raphe nuclei. Of 24 nuclei in the reticular formation, 12 had somatostatin neurons--most notably nuclei gigantocellularis and paragigantocellularis--and only two nuclei, paranigralis and sagulum, did not contain any immunoreactive fibers. In the cerebellum, somatostatin fibers and terminals were restricted to the deep cerebellar nuclei. Of the 11 nuclei projecting to the cerebellum, five contained somatostatin neurons and the majority received somatostatin fibers. Of the limbic system nuclei, somatostatin neurons were confined to the central grey at both pontine and mesencephalic levels. Somatostatin neurons were present in the substantia nigra--compactus and lateralis, but not in reticularis--and absent from the nucleus ruber.(ABSTRACT TRUNCATED AT 400 WORDS)