A single exposure to hyperbaric oxygen (HBO), i.e. pure oxygen breathing at supra-atmospheric pressures causes oxidative DNA base damage both in humans in vivo as well in isolated lymphocytes of human volunteers. This DNA damage, however, is rapidly repaired, and an adaptive protection against further HBO is triggered. Therefore, we tested the hypothesis whether long-term repetitive exposure to HBO would modify the degree of DNA damage. In addition to the measurement of blood antioxidant enzyme activities, the ratio of the oxidized and reduced glutathione content and the level of DNA damage (tail moment in the comet assay) we assessed the DNA damage and superoxide radical (O₂^.-) production induced by a single ex vivo HBO-exposure of isolated lymphocytes. All parameters of oxidative stress and antioxidative capacity in vivo were comparable in the four different groups. Exposure to HBO increased both DNA damage in lymphocytes and O₂^.- production, and this response was significantly more pronounced in the cells obtained from the combat swimmers than in all the other groups. However, in all groups DNA damage was completely repaired within one hours, possibly indicating a higher efficiency of DNA repair in combat swimmers than in the other groups. We conclude that at least in healthy volunteers with endurance training, long-term repetitive exposure to HBO does not modify the basal blood antioxidant capacity or the basal incidence of DNA strand breaks. The increased ex vivo HBO-related DNA damage in isolated lymphocytes from these subjects, however, may reflect enhanced susceptibility to oxidative DNA damage, which is, in turn, more efficiently repaired.