Fluid and electrolyte shifts were measured in seven men (19-21 yr) during three 2-wk bed rest (BR) periods, each of which was separated by a 3-wk ambulatory recovery period. During two of the three BR periods they performed isometric exercise and isotonic exercise. No prescribed exercise was given during the other BR period. On day 4 of BR, plasma volume decreased (P less than 0.05) 441 ml (-12.6%) with no exercise, 396 ml (-11.3%) with isometric, and 262 ml (-7.8%) with isotonic exercise; the decreases (NS) of extracellular volume were -4.4%, -2.6%, and -2.7%, respectively. By day 13 of BR, plasma volume stabilized at the lower level with isometric and isotonic exercise and continued to decline with no exercise; but the extracellular volume returned to or above control levels due to an overshoot of the interstitial volume of +320 to +430 ml (2.0-2.7%) that was about equal to the plasma volume loss. During BR there were isocontent losses from the plasma of protein, albumin, globulin, urea N2, uric acid, creatinine, Na, Cl, osmolarity, P, and glucose that were not influenced by either exercise regimen. However, the blood, red blood cell, and plasma volumes, and the Ca and K contents were stabilized during BR by both exercise regimens. The results suggest that during BR, preservation of the extracellular volume takes precedence over maintenance of the plasma volume, and this mechanism is independent of the effects of isometric or isotonic exercise.