The evolutionary step involving transition from water- to air-breathing exposed the vertebrate cell to an increased risk of becoming acidotic. This is due to the fact that water-breathers generally excrete CO2 more easily than air-breathers. CO2 rapidly diffuses into the cell, where it may result in an excess of hydrogen ions. This is of interest as to the cardiac muscle, since these ions depress contractility, to a large extent probably by inhibiting the inotropic action of calcium ions in a competitive way. The present review, however, concerns the fact that the heart muscle may have an inherent ability to resist the negative inotropic effects of hydrogen ions. This is not a general property of the vertebrate heart, as it shows a clear tendency to be present in most air-breathers, whereas it is absent in most pure water-breathers, i.e. in most fishes. Measurements of the intracellular pH and of the tissue buffer capacity indicate that this ability to maintain force at a normal level in spite of an ongoing CO2-acidosis involves neither neutralization nor excretion of excess hydrogen ions. Instead, studies involving calcium-flux measurements and interventions in the cellular calcium-distribution suggest that the intracellular calcium ion deficit due to acidosis is compensated for by an increase of the calcium pool involved in the beat to beat regulation of cardiac force. How this is accomplished is unclear, although evidence was obtained that mitochondrial calcium stores may be involved.