Maximal O(2) consumption (V(O)(2) max) is an index of integrated cardiopulmonary function. After having defined it, discussed its limitation, and described its measurement, we present data during and after space flight and simulation. During gravity withdrawal, V(O)(2) max stays unchanged. It suddenly drops when the subject is exposed to gravity again and V(O)(2) max is measured upright. Its decrease has a rapid component, attributed to cardiovascular "deconditioning", and a slower component, related to muscle hypotrophy. The cardiovascular adaptation to microgravity and the modalities whereby, upon gravity resumption, it leads to V(O)(2) max drop are discussed. When gravity is resumed, the cardiovascular system does not provide an adequate response to upright exercise, because it is regulated differently from before microgravity exposure. The approach to countermeasures during space flight should change accordingly. Most important becomes ensuring the minimum impact of gravity resumption on the cardiovascular system rather than sustaining V(O)(2) max through aerobic exercise training. Countermeasures centred on gravity application during space flight should be given priority.