Although research has linked the central nervous system with changes in immunoresponsivity, research on the possible role of the central nervous system in altering reticuloendothelial activity is lacking. This study investigated the possible relationship between hypothalamic structures and changes in responsivity of the reticuloendothelial system. Eight male albino rats received bilateral electrode implants in the ventromedial area of the hypothalamus and, following brain stimulation, reticuloendothelial activity was assessed 3, 6, 12, 24, and 96 hours after stimulation. Brain stimulation decreased phagocytic activity of the reticuloendothelial system. These findings may increase our understanding of a possible neural mechanism underlying relationships between stress and resistance to disease states.