This chapter explores immunomodulatory centers in the central nervous system (CNS), used methods in which specific nuclei were electrolytically lesioned, and the effects of these lesions on a variety of both cell-mediated and humoral immune functions were examined. It shows that lesions of the hypothalamus and reticular formation decreased the number of cells in the spleen and caused marked changes the architecture of the thymus. The chapter also shows that electrolytic lesions in the anterior hypothalamus (AHT) decreased the toxic effects of intravenously administered histamine. It examines the effects of AHT lesions on in vitro correlates of cell-mediated immunity. The chapter focuses on the immunologic mechanisms responsible for immune suppression or enhancement following the placement of lesions in the CNS. It also examines the effects of depleting CNS catecholamines by injection of 6-hydroxydopamine, into the cistema magna, or by ablating CNS serotonergic neurons with 5,7 dihydroxytryptamine.