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Data accumulated over 25 years (from 1975 to 2000) on cosmonaut physiological reactions, subjective sensations, and general resistance to G-loads accompanying the orbiting, descent, and landing of Soyuz spacecraft during actual spaceflights are summarized. Materials on short-term (shorter than one month) and long-term (longer than one month) missions in which cosmonauts used or did not use means of preventing microgravity effects during the flight and an anti-G suit (AGS) during descent are analyzed. The physiological reactions of cosmonauts during real spaceflights and terrestrial studies using a centrifuge are compared taking into account cosmonaut ages (from 31 to 55 years). The strain on physiological systems and the reserves of the body upon exposure to +Gx regimens is estimated. A distinct trend toward a lower resistance to descent G-load (without an AGS) with an increase in the time spent in microgravity is found even in the cases when means of prevention of microgravity effects were used. The necessity of using an AGS during descent, irrespective of the flight duration, is demonstrated. The results obtained enable the resistance of cosmonauts to standard G-load conditions during real spaceflights to be predicted.