Developmental changes in activity or expression of transporters may account for alterations in cell behavior as the nonpolarized cell matures. We sought to ascertain whether there is a maturational change in each of the major acid-base transporters in the developing mesangial cell (MC), the Na/H exchanger, Na-dependent Cl/HCO₃ exchanger, and the Cl/HCO₃ exchanger. Intracellular pH (pH_i) was determined by the use of the fluorescent pH-sensitive dye, 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF). We assessed transporter activity by studying recovery from an acid load (NH₄/NH₃) in CO₂/HCO₃. In adult MCs, Na/H exchanger was responsible for 35.2 ± 4.3% of steady-state pH_i, whereas the Na-dependent Cl/HCO₃ exchanger contributed 58.7 ± 6.1 (n = 14). In term MCs (tMCs), from days 1-3 after birth, the Na/H exchanger contributes 62.9 ± 7.8% (n = 11, P < 0.001 vs. adult), whereas the Na-dependent Cl/HCO₃ exchanger contributes 34.0 ± 5.7% (n = 12, P < 0.001 vs. adult), to the rate of recovery from an acid load in these cells. However, in tMCs (days 4-6), the Na/H contributes 47.2 ± 5.9% (n = 8, P < 0.05 vs. adult), whereas the Na-dependent Cl/HCO₃ exchanger contributes 48.7 ± 7.3% (n = 13, P < 0.05 vs. adult), to the rate of recovery. tMCs (days 6-12) yielded transporter activity that was not statistically different than adult MCs (37.8 ± 4.9 and 54.3 ± 10.2% for Na/H and Na-dependent Cl/HCO₃, respectively). The magnitude of the stimulated response to angiotensin II by Na/H and Na-dependent Cl/HCO₃ exchanger in adult and tMCs is unchanged throughout development. The Na/H exchanger appears to play a greater role in pH_i homeostasis earlier on in development, and this may reflect developmental needs of the maturing cell.