Metabolic acidosis (MA) leads to the adaptive increase in renal acid excretion requiring the concerted regulation of metabolic and transport pathways which are only partially understood. Therefore we aim to characterize transcriptonal changes in the kidney during MA. Total kidney RNA from control, 2 and 7 days NH4Cl treated mice was hybridized to Applied Biosystems DNA microarrays and analyzed for transcriptional changes (4 mice each). We identified 100 genes significantly overexpressed and 134 underexpressed (p<0.01, fold change>2 or <0.5) across both time points considered. Microarray results were validated by qRT- PCR of 11 differently regulated genes (PEPCK, SNAT3, AQP2, AQP3, Gls, NaPiIIa, NaPiIIc, Avpr2, Slc4a7, Slc16a2, Slc16a7, Car2) and a high correlation was found. A large group of regulated transcripts represented different solute scarrier transporters (Slc), genes involved in cell growth, proliferation, apoptosis and, as expected, ammoniagenesis. The Wnt signalling pathway regulating kidney development and differentiation, was highly represented in acidotic animals. Interestingly, the majority of acutly -over or undeexpressed genes after 2 days, returned to normal values after 7 days suggesting that adaptation takes then place on a post-transcriptional level.