Mixed metabolic-respiratory acid-base disorders may be diagnosed when the respiratory compensation for a primary metabolic acidosis or alkalosis is inappropriate or when there is inappropriate metabolic compensation for a primary respiratory disorder. The magnitude of the primary change in HCO3 concentration (in metabolic disorders) defines the limits of compensation. We emphasized the importance of the equality of the increment in the anion gap (delta AG) and the decrement in the serum bicarbonate concentration (delta HCO3) in diagnosing a simple high AG metabolic acidosis. The close relationship between these two changes in simple high AG acidoses is reviewed. When the delta HCO3 is greater than the delta AG, we suggest that a mixed high AG and hyperchloraemic acidosis is present. Other possible interpretations of these chemical changes are discussed. When the delta HCO3 is less than the delta AG, a mixed metabolic alkalosis and metabolic acidosis is likely to be present, but other additional explanations of this combination are also reviewed. Thus, guidelines are presented as a basis for the use of the delta AG and delta HCO3 for diagnosing and managing mixed metabolic acid-base disorders.