Carbonic anhydrase (CA) facilitates acid-base transport in several tissues. Acidosis upregulates membrane-bound SDS-resistant hydratase activity in various tissues and CA IV mRNA in rabbit kidney. This study was designed to assess whether the expression of membrane-bound CA IV isozyme in mouse placenta is regulated developmentally and by maternal ammonium chloride loading at the end of pregnancy. For this purpose we used Northern blot analysis, Western blots of microsomal membranes, and immunocytochemistry. The expression of CA IV mRNA on Northern blots tripled from day 11 to day 15 and then remained stable until the end of pregnancy. Expression of CA IV immunoreactive protein on Western blot tripled from day 11 to day 15 and decreased almost to baseline by day 19. Strong staining for CA IV was detected by immunocytochemistry in labyrinthine trophoblast, in the endodermal layer of the yolk sac (both intra- and extraplacental) and in the uterine epithelium. Weak staining was observed in most fetal endothelial cells at 11 days but not later in gestation. Maternal acidosis did not upregulate the expression of CA IV mRNA or CA IV immunoreactive protein. Thus CA IV expression in mouse placenta is developmentally regulated. Maternal acidosis during the last quarter of pregnancy does not upregulate CA IV mRNA or CA IV immunoreactive protein.