The molecular basis for the renal compensation to respiratory acidosis and specifically the role of pendrin in this condition are unclear. Therefore we studied the adaptation of the proximal tubule and the collecting duct to respiratory acidosis. Male Wistar Hannover rats were exposed to either hypercapnia and hypoxia (8% CO₂ and 13 % O₂) (hypercapnic, n=6) or normal air (controls, n = 6) in an environmental chamber for 10 days, and were killed under the same atmosphere. In hypercapnic rats, arterial pH was lower than controls (7.31±0.01 versus 7.39±0.01, p=0.03), blood HCO₃^- concentration was increased (42±0.9 versus 32±0.24 mM, p<0.001), arterial P_CO2 was increased (10.76±0.4 versus 7.20±0.4 kPa, p<0.001), and plasma chloride concentration was decreased (92.2±0.7 versus 97.2±0.5 mM, p<0.001). Plasma aldosterone levels were unchanged. In the proximal tubule, immunoblotting showed an increased expression of NBCe1 protein (188±22% versus 100±11%, p=0.005), confirmed by immunohistochemistry. The total NHE3 protein expression in cortex was unchanged by immunoblotting (119±10 versus 100±11 %, p=0.27) and immunohistochemistry. In the cortex, the abundance of pendrin was decreased (51±9% versus 100±7 %, p=0.003) by immunoblotting. Immunohistochemistry revealed that this decrease was clear both in CCDs and CNTs. This demonstrates that pendrin expression can be regulated in acidotic animals with no changes in aldosterone levels and no external chloride load. This reduction of pendrin expression may help in redirecting the CNT and CCD toward chloride excretion and bicarbonate reabsorption, contributing to the increased plasma bicarbonate and decreased plasma chloride of chronic respiratory acidosis.