We hypothesized that the repetition of brief epochs of hypoxemia in elite human breath-hold divers could induce an adaptation of their metabolic responses, resulting in reduced blood acidosis and oxidative stress. Trained divers who had a 7-10 year experience in breath-hold diving, and were able to sustain apnea up to 440 sec at rest, were compared to control individuals who sustained apnea for 145 sec at the most. The subjects sustained apnea at rest (static apnea), and then, performed two 1-min dynamic forearm exercises whether they breathed (control exercise) or sustained apnea (dynamic apnea). We measured arterial blood gases, venous blood pH, and venous blood concentrations of lactic acid, thiobarbituric acid reactive substances (TBARS), and two endogenous anti-oxidants (reduced glutathione, GSH, and reduced ascorbic acid, RAA). In control subjects, the three experimental conditions elicited an increase in blood lactic acid concentration and an oxidative stress (increased TBARS, decreased GSH and RAA concentrations). In divers, the changes in lactic acid, TBARS, RAA, and GSH concentrations were markedly reduced after static and dynamic apnea, as well as after control exercise. Thus, human subjects involved in a long duration training programme of breath-hold diving have reduced post-apnea as well as post-exercise blood acidosis and oxidative stress, mimicking the responses of diving animals.