Metabolism not only affects the acid–base status of an animal by means of proton stoichiometries but, by feedback regulation, acid–base parameters (pH, [Formula: see text], bicarbonate) influence metabolic rates and the pathways used. This leads to a significant contribution of metabolism to acid–base regulation under both aerobic and anaerobic conditions. The relationship between amino acid metabolism, urea synthesis, and [Formula: see text] excretion is discussed as an example important for steady-state metabolic acid–base regulation during aerobiosis. Generally, acid–base relevant metabolism may be regulated through the effect of acid–base disturbances on hormonal mediation, allosteric modulation of enzyme proteins, pH optima, and the levels of substrates or products, some of these being acid–base relevant substances like bicarbonate, CO2, inorganic phosphate, and NH3. During functional or environmental anaerobiosis the same relationships prevail. Metabolic proton accumulation is counterbalanced by phosphagen depletion and ammonia accumulation in adenylate catabolism. In addition, in integrated control of metabolic and acid–base status, long-term (mitochondrial) anaerobiosis leads to reductions in metabolic rate and increased removal of acidic groups. The importance of metabolic processes in acid–base methodology is discussed in terms of traditional concepts and recent developments.