Angiotensin II (AII) has an important role in the regulation of CRF release. In the present study, the effect of centrally administered AII on CRF messenger RNA (mRNA) levels in the rat hypothalamus was examined. Administration of 0.1 nmol and 1 nmol AII into the lateral ventricle increased the levels of plasma ACTH 20 min and 45 min after administration and those of proopiomelanocortin mRNA in the anterior pituitary (AP) and CRF mRNA in the hypothalamus 2 h after administration. On the other hand, ACTH levels in AP and CRF levels in the median eminence temporarily decreased 45 min after the administration of 1 nmol AII, but it returned to the control level at 90 min. Administration of 10 nmol saralacin, an AII antagonist, blocked 1 nmol AII-induced increase in the levels of plasma ACTH, proopiomelanocortin mRNA in AP, and CRF mRNA in the hypothalamus. These results indicate that central administration of AII increases the CRF mRNA level in the hypothalamus in a receptor-specific manner and also increases CRF release. Therefore, AII seems to have an important role in the regulation of the release and synthesis of CRF in the hypothalamus.