Although increased physical activity early in life is recommended for optimizing bone health, no controlled trials on the effect of activity on bone mass accretion during periods of rapid growth have been reported. The purpose of this study was to determine whether infants randomized to a 1 year gross motor activity program had a greater bone mass accretion than infants randomized to a fine motor activity program. The gross motor program included activities that focused on loading the skeleton and were performed for 15–20 minutes/day, 5 days/week by study personnel. Infants (n = 72) were enrolled at 6 months of age, and total body bone mineral content (BMC), 3-day diet records, and activity levels were obtained at 6, 9, 12, 15, and 18 months. BMC was associated with weight, length, and bone area at all ages and correlated with earlier calcium intakes. Calcium intake appeared to modify the effect of gross motor activity on bone mass accretion; infants in both groups had similar bone accretion at moderately high calcium intakes, but at low calcium intakes infants in the gross motor program had less bone accretion than infants in the fine motor program. Compliant infants in the gross motor group had lower BMC at 18 months compared with noncompliant infants. These results indicate that BMC in infants is related to calcium intake, and we speculate that participation in a gross motor program during rapid bone growth may lead to reduced bone accretion in the presence of a moderate to moderately low calcium intake.