Increasing biochemical evidence suggests that the renin-angiotensin system may be present in may extrarenal tissues. We have employed the mouse submandibular gland renin complementary DNA (pDD-1D2) and the rat liver angiotensinogen complementary DNA (pRang 3) to demonstrate that renin and angiotensinogen messenger RNAs are expressed in the mouse kidney, submandibular gland, heart, adrenal, brain, and testis. To elucidate the factors that influence local tissue renin-angiotensin expressions, we studied tissue renin messenger RNA and enzymatic levels of male mice in response to sodium depletion and castration. Sodium depletion resulted in increased renin expression in the kidney, heart, and adrenal, but not in the submandibular gland and testis. Castration lowered renin levels in all extrarenal tissues but appeared to increase renin level in the kidney. Taken together, the above data demonstrate tissue-specific regulation of renin expression and imply different functions for the sodium responsive and nonresponsive systems.