Exercise during growth and adolescence increases bone mineral density (BMD) in weight-loaded skeletal regions. The development of BMD in unloaded or minimally loaded regions during activity is unclear. We measured BMD in one unloaded, one partly loaded and one highly loaded skeletal region in 67 active soccer players, mean age 22.7 years (range 17-35 years), 128 former soccer players, mean age 54.0 years (range 19-85 years) and 138 controls, mean age 50.6 years (range 19-80 years). The active soccer players played at three different levels: premier league, 3rd league or 6th league. Duration of exercise in these three grou s was 12, 8 and 6 h/week, respectively. BMD (g/cm ) was measured by dual-energy X-ray absorptiometry (DXA) in the upper part of the skull (the unloaded skeletal region), the arms (the partly loaded region) and the femoral neck (the maximal loaded region). Data are presented as mean +/- SD. Active soccer players had 10.3 +/- 10.4% lower BMD in the upper part of the skull (p < 0.001), 1.4 +/- 6.3% higher BMD in the arm (NS) and 12.7 +/- 9.8% higher BMD in the femoral neck (p<0.001) compared with age- and gender-matched controls. All three levels of soccer players demonstrated, independent of activity level, the same discrepancies in BMD compared with controls. Former soccer players had lower BMD in the upper part of the skull until age 70 years and higher BMD in the femoral neck until age 50 years compared with controls. The BMD of the arm was not different in former soccer players compared with controls. In summary, active soccer players had lower BMD in the unloaded skeletal region, no difference in BMD in the partly loaded region and higher BMD in the weight-loaded region compared with controls. The discrepancies compared with controls diminished with age so that no differences were found in BMD after age 70 years. In conclusion, unloaded and weight-loaded skeletal regions may respond differently to increased and decreased physical activity.