The pituitary-adrenal axis is activated during the course of experimental allergic encephalomyelitis (EAE), a paralytic disease resulting from an immunological reaction against central nervous system myelin. The magnitude of the adrenal response not only correlates with the severity of disease, but also serves an important functional role in recovery. We have shown that in EAE there are short-term changes in anterior pituitary pro-opiomelanocortin (POMC) mRNA as well as plasma corticosterone which can be detected before the development of clinical disease. At peak clinical signs when corticosterone and POMC mRNA are maximal, hypothalamic corticotrophin-releasing factor (CRF) mRNA is suppressed, suggesting that pituitary-adrenal activation is not mediated by CRF. Following recovery all parameters return to normal.