The supply of energy is of fundamental importance for the ability to sustain exercise. The maximal duration of exercise is negatively related to the relative intensity both during dynamic and static exercise. Since exercise intensity is linearly related to the rate of energy utilisation this suggests that energetic deficiency plays a major role in the aetiology of muscle fatigue. Characteristic metabolic changes in the muscle are generally observed at fatigue--the pattern being different after short term exercise (lactate accumulation and phosphocreatine depletion) from after prolonged exercise at moderate intensity (glycogen depletion). A common metabolic denominator at fatigue during these and many other conditions is a reduced capacity to generate ATP and is expressed by an increased catabolism of the adenine nucleotide pool in the muscle fibre. Transient increases in ADP are suggested to occur during energetic deficiency and may be the cause of fatigue. Experimental evidence from human studies demonstrate that near maximal power output can be attained during acidotic conditions. Decreases in muscle pH is therefore unlikely to affect the contractile machinery by a direct effect. However, acidosis may interfere with the energy supply possibly by reducing the glycolytic rate, and could by this mechanism be related to muscle fatigue.