According to physicochemical principles, the plasma concentration of hydrogen ions ([H+]), bicarbonate ([HCO3−]), and other acid-base-dependent variables are determined by the plasma PCO2; the strong ion difference ([SID+] = Σ[strong cations] − Σ[strong anions]); and the concentration of weak acids ([ATOT] = [HA] + [A−]). The physicochemical interactions between the acid-base-independent and dependent variables must recognize the constraints imposed by the law of electrical neutrality, dissociation equilibrium of weak acids and water, and the conservation of mass. This review demonstrates the usefulness of the physicochemical approach in studying plasma acid-base control during progressive exercise to exhaustion where the work rate was increased as either a slow (8 W/min) or fast (65 W/min) ramp function. The factors contributing to changes in the concentration of the acid-base-independent variables, and the contribution of the acid-base-independent variables to the plasma [H+] and [HCO3−] during exercise, will be discussed. Key words: PCO2, strong ion difference, weak acids, lactate, potassium
