The distribution of angiotensin II (AII)-immunoreactive cells and fibers was examined in adult male Sprague-Dawley rats with and without colchicine pretreatment. As seems to be the case for a number of other neuropeptides, AII is preferentially found in brain stem, hypothalamic, and limbic structures involved in the control of homeostatic functions. AII-stained cell bodies were most prominent in magnocellular parts of the paraventricular and supraoptic nuclei, and cells were also found in parvocellular parts of the former. Other hypothalamic nuclei containing cell bodies include the suprachiasmatic nucleus, the medial preoptic area, and perifornical parts of the lateral hypothalamic area. Of considerable interest was robust staining in several of the circumventricular organs, in particular the subfornical organ, where both cells and fibers were found. The results of water deprivation and nephrectomy suggest that this staining does not represent uptake of circulating peptide, but instead, represents AII-containing neural connections. In the thalamus, AII-stained cells were found in the paraventricular nucleus, the central medial nucleus, the nucleus reuniens, and rostral parts of the zona incerta. Two cell groups in the basal telencephalon, in the dorsal part of the bed nucleus of the stria terminalis and in the medial nucleus of the amygdala, lay at either end of an AII-stained pathway coursing through the stria terminalis. In the midbrain, immunoreactive cells were found in the interpeduncular and peripeduncular nuclei, and one pontine cell group was detected in the most lateral part of the lateral parabrachial nucleus. The only AII-stained cells in the medulla were in the nucleus of the solitary tract, near the margin of the area postrema. Fibers were found at all levels of the central nervous system, from the olfactory bulbs to the spinal cord, where terminal fields were observed in the substantia gelatinosa and in the intermediolateral cell column. Longitudinally oriented fibers were present throughout the periventricular fiber system and in the medial forebrain bundle, including its caudal extension in ventrolateral parts of the brain stem. It is suggested that, at many different levels, AII serves as both a hormone and neurotransmitter for fluid balance.