Natriuresis induced by extracellular volume expansion (ECVE) is accompanied by a decrease in renin release and by an increase of renal interstitial hydrostatic pressure (RIHP). This study was undertaken to examine, in anesthetized dogs, the relative role of intrarenal angiotensin II (ANG II) changes in mediating natriuresis, diuresis, and increases in RIHP induced by two different levels of volume expansion (1.5 and 5% body wt in 45 min) with isotonic saline. Intrarenal ANG II levels were maintained in the right kidney throughout the experiment by simultaneously infusing captopril (0.8 micrograms.kg-1.min-1) and ANG II (1 ng.kg-1.min-1) into the right renal artery. In response to 5% ECVE, increases in RIHP, natriuresis, and diuresis were inhibited in the right kidney by 55, 40, and 47% respectively, when compared with the left kidney. Significant increases occurred in plasma atrial natriuretic peptide (ANP) levels during 5% ECVE. Maintenance of constant intrarenal ANG II levels during 1.5% ECVE completely abolished the increment of RIHP and diuresis and inhibited the natriuretic response by 80% in the right kidney when compared with the left kidney. Plasma ANP levels did not change during the 1.5% ECVE. No differences between kidneys were found when the intrarenal effects of ANG II were blocked with saralasin before saline loading. These results suggest that increases in RIHP, natriuresis, and diuresis during ECVE are partially mediated by decreases in intrarenal ANG II levels. Furthermore, these results indicate that the role of intrarenal ANG II levels in mediating the renal response to ECVE is more important when plasma ANP levels do not change than when they are increased.