It is known that the renin angiotension system as it is usually understood is not the mediator of experimental one-kidney, one-clip (1K,1C) hypertension in animals. There is also ample evidence that the blood pressure of dogs and rabbits with this form of hypertension can be lowered by immunization with hog renin, which implies that renin is the mediator. In an effort to resolve this contradiction, we searched for a second hypertensive substance which we thought may have been present in the crude hog kidney extracts that had been used to immunize the hypertensive animals. Instead, we ultimately discovered that the blood pressure of hypertensive rabbits could be lowered by immunization with pure hog renin. This remarkable finding could be explained if renin were transformed in vivo, exhibiting new antigenic sites and eliciting a second antihypertensive antibody. We found such an antibody. When free of antirenin, it lowered the blood pressure of 1K,1C hypertensive rabbits. The same antibody stained the cytoplasm of vascular smooth muscle cells and certain other cells in the tissues of normal and hypertensive rabbits. The presence of this transformed renin in the tissues of the rabbit was confirmed by chronic infusion of 125I-labeled renin into hypertensive rabbits. A significant portion of the radioactivity was found to be incorporated into a very high molecular weight, insoluble form. Its function in this location is unknown but must directly or indirectly involve vasoconstriction since its neutralization by specific antibody lowers the blood pressure of 1K,1C hypertensive rabbits.