An analysis of previously published data obtained by our group on patients characterized by markedly slower pulmonary VO₂ kinetics (heart transplant recipients, patients with mitochondrial myopathies, patients with McArdle disease) was carried out in order to suggest that slow VO₂ kinetics should not be considered the direct cause, but rather a marker, of impaired exercise tolerance. For a given ATP turnover rate, faster (or slower) VO₂ kinetics are associated with smaller (or greater) muscle [PCr] decreases. The latter, however, should not be taken per se responsible for the higher (or lower) exercise tolerance, but should be considered within the general concept of "metabolic stability". Good muscle metabolic stability at a given ATP turnover rate (~power output) is associated with relatively smaller decreases, compared to rest, in [PCr] and in the Gibbs free energy of ATP hydrolysis, as well as with relatively smaller increases in [Pi], [ADP(free)], [AMP(free)], and [IMP(free)], metabolites directly related to fatigue. Disturbances in muscle metabolic stability can affect muscle function in various ways, whereas good metabolic stability is associated with less fatigue and higher exercise tolerance. Smaller [PCr] decreases, however, are strictly associated with a faster VO₂ kinetics. Thus, faster VO₂ kinetics may simply be an "epiphenomenon" of a relatively higher metabolic stability, which would then represent the relevant variable in terms of fatigue and exercise tolerance.