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To date, 59 man-EVA's have been conducted in the Shuttle Program with minimum physiological problems or limitations. The physiological requirements for life support in the Shuttle EVA include pressure, gas composition, inspired CO2 pressure, heat- removal capability, in-suit water replacement, and caloric replacement. These requirements and their basis in verification testing or analysis are reviewed. The operational measures are identified. The suit pressure in combination with a gas composition of at least 92 percent assures that sufficient O2 pressure is available to the crewmember. The nominal suit pressure of 4.3 psi±0.1 psi was maintained during all 59 man-EVA's. The contingency suit pressure was never required to be used. The suit pressure in combination with the cabin pressure and pre-EVA denitrogenation procedures minimize the risk of altitude decompression sickness. There has been no incidence of decompression sickness during Shuttle EVA.