The effect of dietary protein on renal function and on renal microvascular reactivity to angiotensin II was determined in rats fed a high-protein diet (40% protein), a low-protein diet (6% protein), or a normal diet (23% protein). Inulin clearance was higher in high-protein-fed rats (n = 7) than in rats fed a low-protein diet (n = 7), 0.88 +/- 0.14 (means +/- SE) vs. 0.54 +/- 0.07 ml.min-1.g kidney wt-1 (P < 0.05). We also used videomicroscopy to assess the effect of angiotensin II on the renal microcirculation in a hydronephrotic kidney preparation. The afferent and efferent arterioles constricted to angiotensin II and norepinephrine in both high- and low-protein-fed rats; this constriction was diminished to angiotensin II but not to norepinephrine, in rats fed a high-protein diet (-24.3 +/- 4.5, -20.2 +/- 4.2%) compared with rats fed a low-protein diet (-39 +/- 5.1, -39.1 +/- 5.7%). The vasoconstrictor responses to angiotensin II in rats fed a high-protein diet and a normal diet were significantly greater following inhibition of angiotensin II formation with captopril but not in low-protein-fed rats. The apparent high-endogenous level of angiotensin II among rats fed a high-protein diet may account for the diminished reactivity to exogenous angiotensin II. Thus alterations in intrinsic vascular reactivity to angiotensin II are not responsible for the altered hemodynamics associated with dietary protein.