Abstract-This study examined the relationships among physical activity, glucocorticoid use, body composition, and bone health in ambulatory women with multiple sclerosis (MS). Twenty-nine white women (mean +/-standard deviation: age 45.1 +/-9.0 yr, Expanded Disability Status Scale 2.9 +/-1.2) diagnosed with MS were assessed for whole body (WB), proximal femur (PF) and lumbar spine (LS) bone status (bone mineral content [BMC], bone mineral density [BMD], and quantitative ultrasound index [QUI] by calcaneal quantitative ultrasound) and body composition by dual energy X-ray absorptiometry; for physical activity by pedometer and accelerometer; and for glucocorticoid medication exposure by selfreport. Accelerometer counts were related to PF BMC (r = 0.50, p = 0.010) when we controlled for age, fat and lean mass, MS disease duration, and glucocorticoid use. Glucocorticoid use was not associated with bone measures. When we controlled for age and fat mass, lean mass was associated with WB BMC (r = 0.41, p = 0.04), PF BMC (r = 0.61, p = 0.001), and speed of sound (SOS) (r = 0.44, p = 0.02), whereas fat mass was associated with SOS and QUI (r =0.43, p = 0.03, and r = 0.44, p = 0.02, respectively). Lean mass was an independent predictor of WB BMC (p = 0.04) and PF BMC (p = 0.001), whereas fat mass was an independent predictor of LS BMD (p = 0.05). In conclusion, physical activity and lean mass are associated with femoral bone mass in women with MS who are ambulatory.