Acidosis had long been thought to influence the bone mineral; however, there was little direct evidence to support this impression. When neonatal mouse calvariae are cultured for 3 hours in medium with a reduced bicarbonate concentration, a model of acute metabolic acidosis, there is net calcium efflux from bone in addition to a net influx of protons into bone lessening the magnitude of the acidosis. The protons appear to exchange for sodium and potassium on the bone surface. In these acute experiments, the calcium efflux appears to be due to mobilization of carbonated apatite through an alteration in the physicochemical driving forces for bone accretion and dissolution. In more chronic cultures (greater than 48 hours) metabolic acidosis induces calcium efflux by stimulating osteoclastic bone resorption and inhibiting osteoblastic bone formation. When calvariae are cultured acutely in medium with an elevated partial pressure of carbon dioxide, a model of respiratory acidosis, there is also calcium efflux, but at the same decrement in pH the magnitude is far less than that observed during metabolic acidosis. There does not appear to be any measurable influx of protons into bone, and during chronic cultures there is no measurable calcium efflux. Thus, acidosis influences the bone mineral; however, for the same decrement in pH there is a marked difference in the response of bone to models of metabolic and respiratory acidosis.