The effects of changes in glomerular filtration rate and renal blood flow on the renal handling of 14C- or 125I-labeled angiotensin II were studied in pentobarbital-anesthetized dogs. Labeled angiotension II was injected as a bolus directly into the renal artery and the renal venous effluent was collected. Under control conditions, 52 ± 8% of the labeled material recovered was angiotensin II and the remaining 48 ± 8% consisted of metabolic products. Reducing glomerular filtration rate by increasing ureteral pressure did not change the percentage of label recovered as angiotension II or metabolic products (54 ± 8% and 46 ± 7% respectively). When renal blood flow was reduced, the percentage of label recovered as angiotensin II fell from 47 ± 6 to 29 ± 7 (P<0.05) and that as metabolites rose from 46 ± 7 to 61± 7 (p<0.05). The heptapeptide des-1-Asp-angiotensin II (angiotensin III) was not found among the metabolites. The results indicate that reductions in glomerular filtration are not important in intrarenal metabolism of angiotensin II in barbiturate anesthetized dogs. However, changes in renal blood flow markedly affect angiotensin II metabolism. These observations are compatible with the notion that the intrarenal metabolism of angiotensin II in the dog occurs mainly in the vascular compartment, rather than in the proximal tubule, and can be regulated by alterations in renal blood flow. Failure to demonstrate angiotensin III in the renal venous effluent suggests that this peptide is not a major circulating product of intrarenal metabolism of angiotensin II in the dog.