The effects of intracellular Ca concentration, [Ca]i, on the volume of rat alveolar type II cells (AT-II cells) were examined. Perfusion with a Ca-free solution induced shrinkage of the AT-II cell volume in the absence or presence of amiloride (1 μM, an inhibitor of Na channels); however, it did not in the presence of 5-(N-methyl-N-isobutyl)-amiloride (MIA, an inhibitor of Na–H exchange). MIA decreased the volume of AT-II cells. Inhibitors of Cl–HCO3 exchange, 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) and 4-acetamido-4′-isothiocyanatostilbene-2,2′-disulfonic acid (SITS) also decreased the volume of AT-II cells. This indicates that the cell shrinkage induced by a Ca-free solution is caused by a decrease in NaCl influx via Na–H exchange and Cl–HCO3 exchange. Addition of ionomycin (1 μM), in contrast, induced cell swelling when AT-II cells were pretreated with quinine and amiloride. This swelling of the AT-II cells is not detected in the presence of MIA. Intracellular pH (pHi) measurements demonstrated that the Ca-free solution or MIA decreases pHi, and that ionomycin increases it. Ionomycin stimulated the pHi recovery after an acid loading (NH4 pulse method), which was not noted in MIA-treated AT-II cells. Ionomycin increased [Ca]i in fura-2-loaded AT-II cells. In conclusion, the Na–H exchange activities of AT-II cells, which maintain the volume and pHi, are regulated by [Ca]i.