Carbonic anhydrase (CA) IV facilitates renal acidification by catalyzing the dehydration of luminal H(2)CO(3). CA IV is expressed in proximal tubules, medullary collecting ducts, and A-intercalated cells of the mature rabbit kidney (Schwartz GJ, Kittelberger AM, Barnhart DA, and Vijayakumar S. Am J Physiol 278: F894-F904, 2000). In view of the maturation of HCO(3)(-) transport in the proximal tubule and collecting duct, the ontogeny of CA IV expression was examined. During the first 2 wk, CA IV mRNA was expressed in maturing cortex and medulla at similar to 20% of adult levels. The maturational increase was gradual in cortex over 3-5 wk of age but surged in the medulla, so that mRNA levels appeared higher than those in the adult medulla. In situ hybridization showed very little CA IV mRNA at 5 days, with increases in deep cortex and medullary collecting ducts by 21 days. Expression of CA IV protein in the cortex and medulla was minimal at 3 days of age but then apparent in the juxtamedullary region, A-intercalated cells and medullary collecting ducts by 18 days; there was little labeling of the proximal straight tubules of the medullary rays. Thus CA IV expression may be regulated to accommodate the maturational increase in HCO(3)(-) absorption in the proximal tubule. In the medullary collecting duct, there is a more robust maturation of CA IV mRNA and protein, commensurate with the high rate of HCO(3)(-) absorption in the neonatal segment.