Scrapie is a transmissible neurodegenerative disease which shares some characteristics with Alzheimer disease (AD). Recent studies show abnormal enlargement of the adrenal glands and kidneys in 139H-affected hamsters. Using immunocytochemical techniques with antibodies to corticotropin-releasing factor (CRF) and vasopressin (VP), we observed the following: (1) a significantly higher number of CRF-immunostained neurons in the preoptic nucleus of hypothalamus of 139H-affected hamsters than controls; (2) the area of VP-immunostained (ir-VP) neurons in the lateral hypothalamus, which includes the internuclear group of magnocellular neurons and the nucleus circularis, was significantly lower for 139H-affected hamsters than for controls; and (3) no significant difference between 139H-affected and control hamsters with regard to the number of ir-VP neurons in the dorsal-medial hypothalamus (DMH), including the paraventricular hypothalamus, or the supraoptic nuclei. However, the population of ir-VP neurons in the DMH shifted to the anterior part of the hypothalamus in 139H-affected hamsters. Three-dimensional models of the immunostaining were prepared and these provide clear depictions of the changes noted. The changes in the CRF and VP systems in 139H-affected hamsters suggest that the neuroendocrine system can be affected by unconventional slow infections.