This study was designed to test the hypothesis that high renal levels of adenosine (ADO) may alter glomerular filtration rate (GFR) control by angiotensin II (ANG II). In normal kidneys, ANG II infusion (20 ng X kg-1 X min-1 iv) decreased renal blood flow (RBF) to 61 +/- 3% of control, increased filtration fraction (FF) to 173 +/- 21% of control, and did not change GFR significantly. During intrarenal ADO infusion at a rate of 1.0 mumol/min, ANG II (20 ng X kg-1 X min-1 iv) decreased RBF and GFR to 61 +/- 5 and 64 +/- 6% of control, respectively. After blocking changes in tubuloglomerular feedback by occluding the ureter during mannitol diuresis, ANG II increased stop-flow pressure and postglomerular resistance (RPG) markedly but did not alter preglomerular resistance (RA), suggesting that the direct actions of circulating ANG II are confined primarily to efferent arterioles in the absence of changes in tubuloglomerular feedback. However, during intrarenal ADO infusion and inhibition of tubuloglomerular feedback, ANG II decreased stop-flow ureteral pressure and raised RA and RPG to 213 +/- 27 and 155 +/- 7% of control, respectively, while decreasing RBF to 59 +/- 5% of control. These observations suggest that ADO markedly alters the control of GFR by ANG II, possibly by causing ANG II to constrict preglomerular vessels, an effect that is not apparent in most physiological conditions but which could play a role in lowering GFR when renal ADO and ANG II levels are both elevated, as in severe renal ischemia.