The present study was performed to examine the role of endogenous bradykinin (BK) in the development of angiotensin II (Ang II)–induced hypertension in mice. BK B₂ receptor knockout (B₂R^−/−) and wild-type (B₂R^+/+) mice (22 to 26 g) were infused with either saline (SAL) or Ang II (40 ng/min) via an osmotic minipump implanted intraperitoneally. On day 12 after implantation, there was no difference in systolic blood pressure (SBP, tail-cuff plethysmography) between SAL/B₂R^+/+ and SAL/B₂R^−/− mice (128±5 versus 133±6 mm Hg, n=24/group). In contrast, SBP was higher on day 12 of infusion in Ang II/B₂R^−/− than in Ang II/B₂R^+/+ mice (173±6 versus 156±5 mm Hg; P<0.05, n=27 and 28). Mean arterial pressure (MAP) was also higher in anesthetized Ang II/B₂R^−/− mice than in Ang II/B₂R^+/+ mice (139±3 versus 124±3 mm Hg; P<0.05, n=16 and 14). Unlike Ang II, long-term norepinephrine (NE) infusion via an osmotic minipump (45 ng/min) caused equivalent increases in SBP in B₂R^+/+ and B₂R^−/− mice measured on day 12 after implantation (151±4 versus 149±5 mm Hg, n=9 and 8). MAP also did not differ on day 13 after implantation between NE/B₂R^+/+ and NE/B₂R^−/− mice (120±6 versus 122±4 mm Hg, n=9 and 8). There were no differences in glomerular filtration rate and urinary sodium excretion among the groups. However, renal plasma flow (RPF) was lower in Ang II/B₂R^−/− mice than in Ang II/B₂R^+/+ mice (2.34±0.06 versus 4.33±0.19 mL · min⁻¹ · g⁻¹; P<0.05). Acute inhibition of NO synthase (NOS) with nitro-l-arginine-methyl ester (0.5 μg · g⁻¹ · min⁻¹) in SAL/B₂^+/+ and SAL/B₂^−/− mice caused equal increases in MAP (142±1 versus 145±1 mm Hg) and decreases in RPF (2.06±0.06 versus 2.12±0.15 mL · min⁻¹ · g⁻¹). However, short-term NOS inhibition caused a greater increase in MAP of Ang II/B₂R^+/+ mice than of Ang II/B₂R^−/− mice, such that MAP after NOS inhibition in Ang II/B₂R^+/+ approached that of Ang II/B₂R^−/− mice (156±2 versus 159±2 mm Hg). These changes were associated with a decrease in RPF in Ang II/B₂R^+/+ mice to values similar to those of Ang II/B₂R^−/− mice before NOS inhibition (2.12±0.09 versus 2.34±0.06 mL · min⁻¹ · g⁻¹). These results demonstrate that the kallikrein-kinin system selectively buffers the vasoconstrictor activity of Ang II. Furthermore, the enhanced susceptibility of B₂R^−/− mice to Ang II–induced hypertension and renal vasoconstriction is likely due to an impaired ability to release NO by endogenous kinins.