The renin substrate, angiotensinogen, was localized by immunocytochemistry in liver and kidney of normal rats by the use of an antiserum directed against pure rat angiotensinogen. This substrate was also examined in rats after bilateral nephrectomy, which is known to increase plasma angiotensinogen, and in rats treated with colchicine, which inhibits serum protein secretion. In normal rat liver, light microscopy showed the presence of immunoreactive material in a very few cells. The number of stained hepatocytes rose in rats treated with colchicine or after bilateral nephrectomy. Immuno-staining increased further when rats were both nephrectomized and colchicine treated. In the kidney, angiotensinogen was specifically located as granular formations in nephrocytes of the proximal tubule but never in the granular cells of the juxtaglomerular apparatus. The localization of these granular formations under the brush border suggests that angiotensinogen is reabsorbed from the glomerular ultrafiltrate rather than synthesized in the kidney.