Angiotensin (ANG) II receptors have been reported in the nonpigmented ciliary epithelium (NPE) of the eye. In cultured NPE, we found ANG II caused a dose-dependent rise of cytoplasmic sodium. The sodium increase was inhibited by the AT₁-AT₂ receptor antagonist saralasin (IC₅₀ = 3.7 nM) and the AT₁ antagonist losartan (IC₅₀ = 0.6 nM) but not by the AT₂ antagonist PD-123319. ANG II also caused a dose-dependent increase in the rate of ouabain-sensitive ⁸⁶Rb uptake. The ANG II-induced cell sodium increase and ⁸⁶Rb uptake increase were reduced by dimethylamiloride (DMA; 10 µM). On the basis of this finding, we propose that Na⁺/H⁺ exchange is stimulated by ANG II. Simultaneously, ANG II appears to inhibit H⁺-ATPase-mediated proton export. Thus Ang II (10 nM) did not alter the baseline cytoplasmic pH (pH_i) but reduced pH_i in cells that were also exposed to 10 µM DMA. Consistent with the notion of H⁺-ATPase inhibition in ANG II-treated NPE, bafilomycin A₁ (100 nM) (BAF) and ANG II were both observed to suppress the pH_i increase that occurs upon exposure to a mixture of epinephrine (1 µM) and acetylcholine (10 µM) and the pH_i increase elicited by depolarization. In ATP hydrolysis measurements, H⁺-ATPase activity (bafilomycin A₁-sensitive ATP hydrolysis) was reduced significantly in cells that had been pretreated 10 min with 10 nM ANG II. In summary, these studies suggest that ANG II causes H⁺-ATPase inhibition and an increase of cell sodium due to activation of Na⁺/H⁺ exchange.