Bone loss during immobilization is well documented. Currently, the only means of studying this in human beings is bed rest, which is resource intensive and inconvenient for the subjects. Unilateral lower limb suspension (ULLS) has been suggested as an alternative, but has not previously been demonstrated to cause bone loss. The main aim of our study was to test the hypothesis that ULLS would cause bone loss determined by peripheral quantitative computed tomography (pQCT). We investigated eight young healthy volunteers (19.1 +/- 0.7 years; body mass index, 22.4 +/- 2.6 kg m(-2)), who underwent ULLS for 24 days; their right foot was suspended with a strap attached to the shoulder so the knee angle was 10 deg and they wore a left shoe with a 7.5 cm sole to allow clearance of the right foot and used bilateral crutches to perambulate. Bone scans were obtained by pQCT from the distal epiphyses and from the diaphyses of the tibia in each leg twice before suspension, at days 7, 14 and 21 of the ULLS, and at days 4, 9, 35 and 90 of recovery. After 21 days of ULLS, bone mineral content of the peripheral portion of the epiphysis of the suspended tibia was reduced by 0.89 +/- 0.48% (from 280.9 +/- 34.5 to 278.4 +/- 34.2 mg mm(-1), P < 0.001) but no changes were observed in its central portion or in the unsuspended tibia. In the peripheral epiphyseal portion, significant bone loss (by 0.32 +/- 0.54%, P = 0.045) occurred as early as day 7 of ULLS. We have demonstrated, for the first time, that in humans bone is lost during ULLS at rates comparable to those seen with bed rest, without alteration in limb fluid volumes thus validating the technique and raising important questions about the mechanisms involved.