The proximal tubule (PT) is major site for the reabsorption of filtered HCO₃^-. Previous work on the rabbit PT showed that: (1) increases in basolateral (BL) [CO₂] raise the HCO₃^- reabsorption rate (J_HCO3), and (2) the increase that luminal Angiotensin II (ANG II) produces in J_HCO3 is greatest at 0% [CO₂]_BL and falls to nearly zero at 20%. Here, we investigate the role of angiotensin receptors in the [CO₂]_BL dependence of J_HCO3 in isolated perfused PTs. We found that, in rabbit S2 PT segments, luminal 10^-8 M saralasin (peptide antagonist of angiotensin II receptors), lowers baseline J_HCO3 (5% CO₂) to the value normally seen at 0% in the absence of inhibitors, and eliminates the J_HCO3 response to changes in [CO₂]_BL. However, basolateral 10^-8 M saralasin has no effect. As with saralasin, luminal 10^-8 M candesartan (AT₁ antagonist) reduces baseline J_HCO3 and eliminates the [CO₂]_BL dependence of J_HCO3. Luminal 10^-7 M PD 123319 (AT₂ antagonist) has no effect. Finally, we compared PTs from wild-type and AT_1A-null mice of the same genetic background. Knocking out AT_1A modestly lowers baseline J_HCO3 and, like luminal saralasin or candesartan in rabbits, eliminates the J_HCO3 response to changes in [CO₂]_BL. Our accumulated evidence suggests that Ang II endogenous to the PT binds to apical AT_1A receptor, and that this interaction is critical for both baseline J_HCO3 and its response to changes in [CO₂]_BL. Neither apical AT₂ receptors nor basolateral Ang II receptors are involved in these processes.