Previous authors showed that, at low doses, both basolateral and luminal ANG II increase the proximal tubule's HCO(3)(-) reabsorption rate (J(HCO(3))). Using out-of-equilibrium CO(2)/HCO(3)(-) solutions, we demonstrated that basolateral CO(2) increases J(HCO(3)). Here, we examine interactions between ANG II and CO(2) in isolated, perfused rabbit S2 segments. We first used equilibrated 5% CO(2)/22 mM HCO(3)(-)/pH 7.40 in bath and lumen. At 10(-11) M, basolateral (BL) ANG II increased J(HCO(3)) by 41%, and luminal ANG II increased J(HCO(3)) by 35%. At 10(-9) M, basolateral ANG II decreased J(HCO(3)) by 43%, whereas luminal ANG II was without effect. Second, we varied [CO(2)](BL) from 0 to 20% at fixed [HCO(3)(-)](BL) and pH(BL). Fractional stimulation produced by BL 10(-11) M ANG II falls when [CO(2)](BL) exceeds 5%. Fractional inhibition produced by BL 10(-9) M ANG II tends to rise when [CO(2)](BL) exceeds 5%. Regarding luminal ANG II, fractional stimulation produced by 10(-11) M ANG II fell monotonically as [CO(2)](BL) rose from 0 to 20%. Fractional inhibition produced by 10(-9) M ANG II rose monotonically with increasing [CO(2)](BL). Viewed differently, ANG II at 10(-11) M tended to reduce stimulation by CO(2), and at 10(-9) M, produced an even greater reduction. In conclusion, the mutual effects of 1) ANG II on the J(HCO(3)) response to basolateral CO(2) and 2) basolateral CO(2) on the J(HCO(3)) responses to ANG II suggest that the signal-transduction pathways for ANG II and basolateral CO(2) intersect or merge.