We induced metabolic alkalosis and acidosis in 10 healthy volunteers in order to analyse in vivo relation between pH and ionized calcium (cCa2+). In the alkalinization test, 2.7 mol/kg NaHCO3 was injected. In the acidification test, volunteers took 4 mmol/kg NH4Cl. Blood pH and cCa2+ (mmol/l) mean values (SD) baseline, after alkalinization and acidification tests, were: 7.363 (0.018), 7.456 (0.031), 7.244 (0.031), 1.27 (0.03), 1.14 (0.03) and 1.38 (0.04). Mean slope of regression log cCa2+/pH was -0.39 (SD 0.11). Such a slope differs after in vivo or in vitro changes, due to the in vivo rapid restoration of equilibrium between the plasmatic and interstitial compartments following changes in water and electrolyte concentrations. The type of acid-base alteration-respiratory or metabolic-influences pH changes, and consequently the regression slope. The in vivo slope for log cCa2+/pH in normal subjects (-0.21) is much the same as in acute respiratory alterations (-0.17), whereas it differs in acute metabolic alterations (present study). Bicarbonates play different roles: the same changes in pH cause greater changes in cCa2+ after acute metabolic rather than respiratory alterations. Ca2+ homeostasis is maintained in acute respiratory acid-base imbalance, despite wide shifts in pH, whereas in acute metabolic alterations even small pH changes have striking repercussions on cCa2+. The experimental angular coefficient for in vivo acute metabolic acid-base alterations differs from the theoretical one calculated by Thode's differential equation (-0.25).