Recent studies employing molecular biological techniques demonstrate that renin and angiotensinogen genes are expressed in various tissues. We have observed tissue-specific regulation of renin and angiotensinogen gene expressions. Renin expression in kidney, heart, and adrenal are stimulated by sodium depletion and beta-adrenergic agonist. Submandibular gland and genital renins are not. Instead, the renin expression in these tissues are influenced by androgen and/or hormones that are activated during ontogeny. Genetic influence of tissue renin expression also exists, i.e., the submandibular gland, cardiac, and testicular renin activities are higher in the two gene strains, whereas kidney renin activity does not differ between different strains. Tissue-specific regulation of angiotensinogen mRNA is also observed when rats are placed on a low-sodium diet. Sodium depletion stimulates renin angiotensinogen mRNA expression but does not influence hepatic angiotensinogen mRNA levels. Tissue-specific regulation of renin angiotensin may have important functional implications. Increased local production of angiotensin should influence tissue angiotensin-mediated responses that may be independent of the circulating system.