In previous experiments on the isolated rabbit kidney perfused with a medium free from renin substrate (RS) we have shown that addition of RS resulted in an increase in renal vascular resistance (RVR) , glomerular filtration rate (GFR), and filtration fraction (FF) ( 1 ) . Since these experiments were performed in a recirculating perfusion system, it was not possible to decide whether renin had reacted with its substrate within the kidney or outside of it. To obtain better information on the site of enzymesubstrate reaction, an "open" perfusion system without recirculation was developed for the rat kidney. In such a preparation, intrarenal renin can act with RS added to the perfusion fluid only within the kidney. It is also possible to compare the hemodynamic effects elicited by intrarenal infusion of angiotensin I or I1 with those observed after addition of RS.Materials and Methods. Male Sprague-Dawley rats weighing between 180 and 240 g were anesthetized with sodium pentobarbital (50 mg/kg ip) . After catheterization of the right ureter, ligatures were placed around the inferior vena cava and around the aorta proximal and distal to the right renal vessels. Immediately after ligation of the aorta proximal to the right renal artery, perfusion was started via a catheter inserted into the mesenteric artery. Renal venous effluent was collected by a catheter placed in the inferior vena cava, and renal "plasma" flow (RPF) was measured by a dropcounter at this site. A cannula was inserted into the aorta distal to the right renal artery and connected to a transducer (Statham P 23 Db). Flow of the perfusate and perfusion pressure (PP) were continuously recorded.By means of a peristaltic pump (Harvard App., Model 1203) perfusion medium was carried from a reservoir into a plastic disc oxygenator equilibrated with a gas mixture of 95% O2 and 5% COZ and from there, via a bubble trap and a damping chamber, to the kidney that was placed in a warmed holder (37") and covered with paraffin oil.As perfusion medium Krebs-Henseleit solution was used, modified by the addition of 35 g/liter Haemaccel (Behringwerke, Marburg), 6 mM urea, 2 mM sodium pyruvate, 1 mlM sodium oxalacetate, 10 mg/liter neomycin sulfate, 500 mg/liter inulin, 20 mg/liter PAH? and 20 mU/liter vasopressin.Before the perfusion medium was filled into the system, it was filtered by means of a membrane filter with a pore size of 0.45 pm (Sartorius, Gijttingen)