The renin-angiotensin system is a classic endocrine system that also exists within individual tissues. All components of the renin-angiotensin system (RAS) are expressed in the kidney suggesting the potential for local production and action of angiotensin II. Although the importance of the kidney in hypertension is unequivocal, our understanding of the functional significance of intrarenal production of angiotensin II remains incomplete. Using genetic manipulation of the mouse genome we generated a novel transgenic model expressing human angiotensinogen specifically in the proximal tubule cells of the kidney. Herein I describe the generation and physiologic characterization of this model, and discuss the implications of our findings in terms of the genetics of human hypertension. The experimental results presented support the hypothesis that a tissue-specific RAS cascade exists in the kidney of this transgenic model, and that this system may play an important role in blood pressure (BP) and renal homeostasis in this model.