Over the last decade, gene targeting technologies have provided investigators with powerful new tools to study the physiology and pathophysiology of the kidney. In that, the renin-angiotensin system (RAS) has been a subject of intense investigation. Detailed analyses of mutant mice have not only confirmed notions already suggested by other studies, but also shed a new light on previously unrecognized functions of RAS. In this review, we will focus on what we have learned from these gene targeted animals in particular relevance to nephrology.(Internal Medicine 38: 315-323, 1999)