In the collecting duct, the fine-tuning of salt and acid-base homeostasis is regulated by transport proteins located in two different cell types, intercalated and principal cells. During acidosis, acid-secretory intercalated cells proliferate which may contribute to the remodelling of the collecting duct. The aim of this study was to investigate the adaptive response in the collecting duct to metabolic alkalosis. Mice were subjected to either normal tap water (control), 0.28 mmol/L NaCl or 0.28 mmol/L NaHCO₃ in drinking water for either 12 hours, 24 hours, 2 days, or 7 days, respectively. Quantitative real-time rt-PCR was performed for AE1, pendrin, AQP2, Foxi1, GDF-15, and CP2L1. Western blotting was performed for AE1, pendrin, and AQP2. Pendrin mRNA abundance was significantly increased after 24 hours of alkali load. In contrast, AE1 mRNA levels were diminished after 12 hours in NaHCO₃ treated mice and NaCl treated mice. AQP2 mRNA abundance was markedly increased in the NaHCO₃ group compared to control and NaCl treated animals. Notably, protein abundance of AE1 was decreased after 24 hours, pendrin protein expression was not different between groups, and AQP2 protein levels were significantly elevated after 24 hours, 2 and 7 days. Foxi1, GDF-15, and CP2L1 have been reported to be involved in intercalated cell proliferation and differentiation. Foxi1 mRNA levels were increased after 24 hours and 2 days, and GDF-15 after 2 days alkali load. In conclusion, during alkalosis key acid base transport proteins in the collecting duct are regulated. Transcription factors may have an impact on this adaptive response.