The local, direct effect of endogenous angiotensin II (AII) in the isolated, perfused rat kidney was studied in an "open-circuit," single-pass preparation perfused at a constant pressure with an artificial solution containing 6.5% bovine albumin in Krebs-Ringer solution. After the addition of purified renin substrate (tetradecapeptide, 3 to 5 X 10(-8) M), renal plasma flow fell from 25.3 +/- 1.6 to 14.4 +/- 1.0 ml x min-1 (N = 6, P < 0.001) and GFR rose from 0.3 +/- 0.03 to 0.63 +/- 0.06 ml.min-1 (P < 0.001). Filtration fraction rose accordingly from 0.015 +/- 0.001 to 0.044 +/- 0.002 (P < 0.001). The effects of the renin substrate were promptly reversed by the addition of an angiotensin antagonist, Sar1-Al8-AII (3 X 10(-6) M). Measurements of distribution of perfusate flow between outer and inner cortex were made with radioactive microspheres. Outer cortical flow was 75.3 +/- 3.5% of the total cortical flow during the control periods and 73.7 +/- 2.3% during the maximal renin substrate effect. We conclude that endogenous AII is active locally, independent of systemic recirculation. Its major site of action in this preparation is on the efferent glomerular arteriole.