The supraspinal afferent and efferent connections of the A5 noradrenergic cell group were examined in rats. Very small deposits of HRP-WGA were made in the rostral A5 area. Catecholamine histofluorescence techniques were used to confirm that the deposits overlapped the A5 column. Retrogradely labeled cells were present in the perifornical area and paraventricular nucleus of the hypothalamus, the Kölliker-Fuse nucleus, dorsal parabrachial area, intermediate and caudal portions of the nucleus of the solitary tract, and the ventral medullary reticular formation in the areas of the A1 and B1 cell groups. Anterograde HRP-WGA labeling was found in several areas of the subcortical CNS. The contribution of A5 neurons to this labeling was confirmed with retrogradely transported fluorescent latex microspheres combined with catecholamine histofluorescence techniques. The A5 cell group was found to have significant projections to the central nucleus of the amygdala, perifornical area of the hypothalamus, midbrain periaqueductal gray, parabrachial area, and the nucleus of the solitary tract. Other A5 projections include the paraventricular nucleus of the thalamus, the bed nucleus of the stria terminalis, and possibly the zona incerta and lateral and dorsal hypothalamic areas. In addition, A5 neurons may innervate the ventrolateral reticular formation of the medulla. Virtually all of the areas innervated by A5 noradrenergic neurons are involved in cardiovascular regulation. In addition, the A5 area receives afferent input from major cardiovascular regulatory centers of the supraspinal CNS. Thus the A5 cell group has the potential to exert a significant influence on the cardiovascular regulatory system.