A meta-analysis of adult exercise studies and an infant activity trial show a possible interaction between physical activity and calcium intake on bone. This randomized trial of activity and calcium supplementation was conducted in 239 children aged 3-5 years (178 completed). Children were randomized to participate in either gross motor or fine motor activities for 30 minutes/day, 5 days per week for 12 months. Within each group, children received either calcium (1000 mg/day) or placebo. Total body and regional bone mineral content by DXA and 20% distal tibia measurements by peripheral quantitative computed tomography (pQCT) were obtained at 0 and 12 months. Three-day diet records and 48-h accelerometer readings were obtained at 0, 6, and 12 months. Higher activity levels were observed in gross motor versus fine motor activity groups, and calcium intake was greater in calcium versus placebo (1354 +/- 301 vs. 940 +/- 258 mg/day, p < 0.001). Main effects of activity and calcium group were not significant for total body bone mineral content or leg bone mineral content by DXA. However, the difference in leg bone mineral content gain between gross motor and fine motor was more pronounced in children receiving calcium versus placebo (interaction, p = 0.05). Children in the gross motor group had greater tibia periosteal and endosteal circumferences by pQCT compared with children in the fine motor group at study completion (p < 0.05). There was a significant interaction (both p < or = 0.02) between supplement and activity groups in both cortical thickness and cortical area: among children receiving placebo, thickness and area were smaller with gross motor activity compared with fine motor activity, but among children receiving calcium, thickness and area were larger with gross motor activity. These findings indicate that calcium intake modifies the bone response to activity in young children.