Presently, exercise protocols and equipment for spaceflight are unresolved, although recent calculations suggest that all exercise in space to date has lacked sufficient loads to maintain preflight musculoskeletal mass. We hypothesized that lower body negative pressure (LBNP) produces a footward force equal to the product of the pressure differential and body cross-sectional area at the waist seal. Twelve male volunteers weighing 67.6-86.9 kg were sealed at the superior iliac crest in upright and supine LBNP chambers. Neither configuration included a saddle, so that the force due to LBNP was transmitted to the feet of our subjects. Each subject was exposed to 10 mm Hg increments of LBNP up to 70 mm Hg (standing) or to 50-100 mm Hg (supine), depending upon individual tolerance. Static reaction force was measured at each LBNP level for approximately 1-2 min. An additional static force approximately equivalent to 1% Earth body weight was generated against the feet by each mm Hg of LBNP either during upright standing or supine posture. Furthermore, the forces measured during LBNP agreed well with forces calculated from the cross-sectional areas of our subjects' waists. These results indicate that exercise in microgravity against 100 mm Hg LBNP could produce static and inertial forces similar in magnitude to those occurring on Earth. This gravity-independent technique may help maintain the musculoskeletal and cardiovascular systems of crewmembers during prolonged exposure to microgravity.