Distal renal tubular acidosis (dRTA) is caused by impaired excretion of acid in the renal collecting duct and affects systemic mineral and electrolyte balance. A protein rich Western diet constitutes a physiological acid-load which requires increased urinary acidification. Patients with mutations in the intercalated cell specific B1 subunit of the vacuolar H+-ATPase suffer from dRTA. Recently we described a mouse model lacking the B1 subunit with impaired urinary acidification. WT and B1 KO mice were fed over 10 weeks with a normal (NP, 20 %) or high protein (HP, 50 %) diet. Surprisingly, B1 KO grew more on the HP and increased blood pH and bicarbonate levels. Urinary pH was more alkaline in the B1 KO. WT animals responded with an increased urinary excretion of Na, Cl, P, whereas B1 KO had low excretion rates. Thus, the physiological acid load with a HP diet does not lead to dRTA in mice lacking the B1 subunit and possibly triggers a complex compensatory mechanism.