Hypoventilation increases PaCO2 (hypercapnia) and initiates the acid-base disorder known as respiratory acidosis. Hyperventilation decreases PaCO2 (hypocapnia) and initiates the acid-base disorder known as respiratory alkalosis. The impact on acidity of these primary changes in PaCO2 is ameliorated by secondary, directional changes in plasma bicarbonate concentration that occur in two stages. Acutely, modest changes in plasma bicarbonate originate from titration of the body’s nonbicarbonate buffers. In chronic hypercapnia and hypocapnia, larger changes in plasma bicarbonate occur that reflect adjustments in renal acidification mechanisms. As a result, the amelioration of systemic acidity is more pronounced in the chronic forms of the respiratory acid-base disorders.