The efferent connections of the parabrachial nucleus have been analyzed in the rat using the anterograde autoradiographic method. Fibers originating from the lateral parabrachial nucleus (PBl) ascend in the periventricular system, the dorsal tegmental bundle and the central tegmental tract. The PBl projects to the dorsal raphe nucleus, the superior central raphe nucleus, and the Edinger-Westphal nucleus. It also innervates the intralaminar (centromedian, centrolateral, paracentral, parafascicular), the midline (paraventricular, reuniens), and the ventromedial basal (VMb) thalamic nuclei as well as much of the hypothalamus, including the dorsomedial, the ventromedial, the arcuate and the paraventricular nuclei, the lateral hypothalamic and the lateral preoptic areas. The PBl sends fibers via the ansa peduncularis into the amygdala, innervating the anterior, the central, the medial, the basomedial, and the posterior basolateral nuclei. In addition, it projects to the lateral part of the bed nucleus of the stria terminalis. Descending PBl fibers travel mainly through the ventrolateral medulla, passing through the region of the A1 and A5 catecholamine cell groups, the ventrolateral reticular formation and the region that contains parasympathetic preganglionic neurons. A small component travels in Probst's bundle to the ventral part of the nucleus of the solitary tract. Only a few PBl axons continue caudally into the lateral funiculus of the spinal cord, but these could not be followed beyond the first few cervical segments. The projections of the medial parabrachial nucleus (PBm) are similar to those of PBl, but two major differences have been noted. One difference is that the PBm provides a direct input to 4 regions of cerebral cortex: (1) the granular insular cortex; (2) the deep layers of the frontal cortex; (3) the septo-olfactory area; and (4) the infralimbic cortex. The other difference is that unlike the PBl, the PBm appears to provide almost no input to the medial hypothalamic nuclei (dorsomedial, ventromedial, arcuate nuclei) nor to the medial amygdaloid nucleus. The PBm projects heavily to the nucleus ambiguus and there was no evidence for an input to the nucleus of the solitary tract. The projections of the Kölliker-Fuse nucleus (KF) are distinct from those of either PBm or PBl. The KF projects via the central tegmental tract to the lateral hypothalamic area, the lateral preoptic area, and the central nucleus of the amygdala. The contralateral projection to the zona incerta, the lateral hypothalamic area, and the lateral preoptic areas is more prominent than the ipsilateral projections. Descending KF fibers travel mainly through the ventrolateral medullary reticular formation passing through regions which give rise to parasympathetic preganglionic fibers of the VIIth, IXth and Xth cranial nerves and the A1 and A5 catecholamine cell groups. In one experiment, fibers could be followed to the intermediolateral cell column of the upper thoracic spinal cord.