Chronic angiotensin II (Ang II) infusions enhance urinary excretion of angiotensinogen, suggesting augmentation of distal nephron sodium reabsorption. To assess whether chronic Ang II infusions (15 ng/min for 2 weeks) enhance distal nephron sodium reabsorption, we compared sodium excretion before and after blockade of the 2 main distal nephron sodium transporters by IV amiloride (5 mg/kg of body weight) plus bendroflumethiazide (12 mg/kg of body weight) in male C57/BL6 anesthetized control mice (n=10) and in chronic Ang II–infused mice (n=8). Chronic Ang II infusions increased systolic blood pressure to 141±6 mm Hg compared with 106±4 mm Hg in control mice. After anesthesia, mean arterial pressure averaged 97±4 mm Hg in chronic Ang II–infused mice compared with 94±3 mm Hg in control mice, allowing comparison of renal function at similar arterial pressures. Ang II–infused mice had lower urinary sodium excretion (0.16±0.04 versus 0.30±0.05 μEq/min; P<0.05), higher distal sodium reabsorption (1.74±0.18 versus 1.12±0.18 μEq/min; P<0.05), and higher fractional reabsorption of distal sodium delivery (91.1±1.8% versus 77.9±4.3%; P<0.05) than control mice. Urinary Ang II concentrations, measured during distal blockade, were greater in Ang II–infused mice (1235.0±277.2 versus 468.9±146.9 fmol/mL; P<0.05). In chronic Ang II–infused mice treated with spironolactone (n=5), fractional reabsorption of distal sodium delivery was similarly augmented as in chronic Ang II–infused mice (94.6±1.7%; P<0.01). These data provide in vivo evidence that there is enhanced distal sodium reabsorption dependent on sodium channel and Na⁺-Cl⁻ cotransporter activity and increased urinary Ang II concentrations in mice infused chronically with Ang II.