Oxygen prebreathe (PB) before decompression eliminates dissolved nitrogen and therefore decreases the risk of decompression sickness (DCS) in aviators and astronauts. Factors that effect tissue perfusion, such as body position, temperature and exercise are known to increase denitrogenation kinetics during oxygen breathing. Only two hours of ground level denitrogenation, with light exercise (oxygen consumption 0.3-0.4 1/min) prior decompression from 760 to 220 mm Hg are enough to protect 70 sitting subjects against severe DCS during 4 hour simulation of extravehicular activity (with oxygen consumption 1.0-1.5 1/min) at off-nominal pressure mode. However, two hours of oxygen prebreathing are not enough to protect 30 test subjects against DCS during 2 hours exposure with metabolic rate (MR) 5-8 kcal/min (oxygen consumption 1.0-1.5 1/min) at emergency pressure level 145 and 198 mm Hg. In this case severe bends occurred after 30 minutes of exposure at this emergency pressure mode.The on-ground experimental study of denitrogenation by oxygen breathing through an oxygen mask showed that two-hours denitrogenation was inadequate only if the breathing gas contained about 10 % nitrogen or if the process included 3-10 minutes of air breathing interruptions. Reducing the nitrogen content in breathing gas to 0.4-5.0 % eliminated severe symptoms of the DCS and decreased significantly the incidence of its mild forms to 3.2 % at 220 mm Hg during a 4 hour exposure with arm and leg exercises. There was 10 % of DCS incidence at 145 and 198 mm Hg during 2 hours exposure with upper and lower limb activity. This allowed work of moderate load at the ambient pressure 220 mm Hg without failure after two-hour breathing of oxygen with nitrogen admixture no more than 5 %.