Acidosis has important effects on the bone mineral which can be investigated utilizing neonatal mouse calvariae in organ culture. When calvariae are cultured for 3 h in physiologically acidic medium produced by a reduction of the bicarbonate concentration, a model of acute metabolic acidosis, there is net calcium efflux from bone in addition to net proton influx into bone which lessens the severity of the acidosis. Utilizing a high resolution scanning ion microprobe to study the bone during acidosis we have found that the protons exchange for sodium and potassium on the bone surface. In acute experiments the calcium efflux is the result of mobilization of carbonated apatite through an alteration in the physicochemical driving forces for bone mineral accretion and dissolution. In the more chronic cultures (greater than 48 h) metabolic acidosis induces calcium efflux by stimulating osteoclastic bone resorption and inhibiting osteoblastic bone formation. When calvariae are cultured for 3 h in acidic medium produced by an increase in the partial pressure of carbon dioxide, a model of respiratory acidosis, there is also calcium efflux; however, at the same decrement in pH the net flux is far less than that observed during metabolic acidosis. During acute respiratory acidosis there is no measurable influx of protons into bone and during chronic studies there is no measurable calcium efflux.