Abstract Microinjection of l-glutamate into a subregion of the gigantocellular nucleus of the rat medulla oblongata significantly lowers arterial pressure. This vasodepressor area, the gigantocellular depressor area, is topographically distinct from other vasoactive areas of the medulla. We sought to determine the efferent projections of the gigantocellular depressor area and compare these to the efferent projections of sympathoexcitatory neurons within the rostral ventrolateral medulla. The anterograde tracer Phaseolus vulgaris-leucoagglutinin was deposited into sites in the gigantocellular depressor area or rostral ventrolateral medulla (pressor area) functionally defined as vasodepressor or vasopressor by microinjections of l-glutamate. Following Phaseolus vulgaris-leucoagglutinin injections into the gigantocellular depressor area, labeled punctate fibers were seen bilaterally within distinct areas of a number of autonomic regions including the nuclei of the solitary tract, subcoeruleus area, parabrachial complex, the medial medullary reticular formation of the medulla and pons, and laminae 7 and 10 of the thoracic spinal cord. Following deposits into the rostral ventrolateral medulla (pressor area), labeled fibers were seen in many of these same autonomic nuclei; however, efferents from the gigantocellular depressor area to the nucleus of the solitary tract, the parabrachial complex and the reticular formation were medial to rostral ventrolateral medulla (pressor area) efferents to these same areas. These data indicate that neurons within the gigantocellular depressor area and the rostral ventrolateral medulla (pressor area) project to autonomic nuclei throughout the central nervous system and further suggest a heterogeneity of function with regard to autonomic control both within the reticular formation and its efferent targets. In addition, these data support the view that the gigantocellular depressor area may be a novel reticulpspinal sympathoinhibitory area.