We applied the neuroanatomical tracers cholera toxin-horseradish peroxidase and wheat germ agglutinin-horseradish peroxidase to investigate the neural connections of the area postrema (AP) in the rat. We find that the AP projects to the nucleus of the solitary tract (NTS) and dorsal motor nucleus of the vagus bilaterally both rostral and caudal to obex; the nucleus ambiguus; the dorsal aspect of the spinal trigeminal tract and nucelus and the paratrigeminal nucleus; the region of the ventrolateral medullary catecholaminergic column; the cerebellar vermis; and a cluster of structures in the dorsolateral pons which prominently include a discrete set of subnuclei in the lateral parabrachial nucleus. The major central afferent input to the area postrema is provided by a group of neurons in the paraventricular and dorsomedial hypothalamic nuclei whose collective dendrites describe a horizontally oriented plexus which encircles the parvocellular nucleus of the hypothalamus bilaterally. In addition, the caudal NTS may project lightly to the AP. The lateral parabrachial nucleus provides a very light input as well. These connections, when considered in the context of the known vagal afferent input and reduced blood-brain barrier of AP, place this structure in a unique position to receive and modulate ascending interoceptive information and to influence autonomic outflow as well.