Corticotropin-releasing hormone (CRH) is a central mediator in the response to stress, coordinating behavioral, autonomic and neuroendocrine activation. CRH overproduction is implicated in several affective disorders, including major depression, panic-anxiety disorder and anorexia--diseases also associated with altered immune function. We investigated the link between CRH overdrive and immune function using CRH transgenic mice. Following immunization, CRH transgenic mice fail to form germinal centers; chronic glucocorticoid administration recapitulates this effect in wild-type mice. Regulation of germinal centers by glucocorticoids appears to be mediated, in part, through effects on follicular dendritic cells (FDC), providing a novel mechanism by which CRH dysregulation may significantly impair humoral immune responses.