The endocrine response to surgical stress results in activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. The cellular response to a wide variety of stresses results in the synthesis of a family of stress response proteins termed heat shock proteins. Potential interactions between endocrine and cellular stress responses have not been investigated in vivo. A surgical model was developed to define the genetic response to surgical stress. Wistar rats underwent ether anesthesia, laparotomy, hemorrhage, and variable recovery periods. Tissues were subsequently harvested and the RNA was isolated and probed for HSP70 messenger RNA levels. These studies showed a strong induction of HSP70 but only in the adrenal gland, aorta, and vena cava. This specific induction was rapid, occurring 30 minutes after surgery, and dramatic (greater than twentyfold induction). The induction occurred in parallel with HPA axis activation and was adrenal cortical specific as determined by in situ hybridization. These observations suggest a functional interaction between the molecular stress response and HPA axis activation.