It has been convincingly demonstrated that the in vivo immune response is not fully autonomous. Clearly, functional interactions exist between the neuroendocrine system and the immune system that operate during the generation of normal in vivo immune responses. In addition to playing an important regulatory role in the absence of perturbation, the same neuroendocrine signals that facilitate immune function in a nonstressed organism may suppress immune function in a physiologically or psychologically stressed organism. Given the complexity of these interactions, the current paper will focus on neuroendocrine modulation of one important dimension of acquired immunity, the in vivo antibody response to a benign protein (keyhole limpet hemocyanin, KLH). In addition, only the hypothalamic-pituitary-adrenal (corticosterone) response and the sympathetic nervous system (norepinephrine and epinephrine) response will be discussed. The current paper will 1) examine the cellular steps involved in the antibody response to KLH; 2) describe the specific cellular consequences of acute stressor exposure on this response; 3) describe the evidence for corticosterone and catecholamine modulation of the in vivo antibody response during quiescent and stressed states; and 4) present data that support the hypothesis that regular, moderate, physical activity can prevent the neuroendocrine and detrimental immunological effects of stress.