Study Design. We measured the cross-sectional area of the intervertebral discs of normal volunteers after an overmight rest; before, during, and after 5 or 17 weeks of bed rest; and before and after 8 days of weightiessness. Objectives. This study sought to determine the degree of expansion of the lumbar discs resulting from bed rest and space flight. Summary of Background Data. Weightlessness and bed rest, an analog for weightlessness, reduce the mechanical loading on the musculoskeletal system. When unioded, intervertebral discs will expand, increasing the nutrtional diffusion distance and altering the mechancial properties of the spine. Methods. Magnetic resonance imaging was used to measure the cross-sectional area and transverse relaxation time (T2) of the intervertebral discs. Results. Overnight or longer bed rest causes expansion of the disc area, which reaches an equilibrium value of about 22% (range 10–40%) above baseline within 4 days. Increases in disc area were associated with modest increases in disc T2. During bed rest, disc height increased approximately 1 mm, about one-half of previous estimates based on body height measurements. After 5 weeks of bed rest, disc area returned to baseline within a few days of ambulation, whereas after 17 weeks, disc area remained above baseline 6 weeks after reambulation. After 8 days of weightlessness, T2, disc area, and lumbar length were not significantly different from baseline values 24 hours after landing. Conclusions. Significant adaptive changes in the intervertebal discs can be expected during weightlessness. These changes, which are rapidly reversible after short duration flights, may be an important factor during and after long-duration missions.