The effect of functional activity on bone formation and interstitial fluid space in a standardized tibial defect was measured in 19 dogs with one hind limb elevated and the other weight bearing and in 15 dogs bearing weight on all four legs. The interstitial fluid space (V(isf)) of the woven bone of the weight-bearing defect was larger than that in the elevated legs at seven and 14 days. By 28 days, this difference disappeared. In a third group of six dogs, medullary canal pressure was measured in the immobilized and weight-bearing tibias. The pressures were higher in the weight-bearing tibiae at two, three, four, and five days. Because the increase in V(isf) in the weight-bearing defects coincided with the onset of woven bone formation in the defects and an increase in medullary canal pressure, an increase in venous pressure could increase capillary pressure and capillary filtration. Such an increase in filtration might cause the larger V(isf) in the weight-bearing defects and better capillary perfusion of precursor cells of the osteoblast. A hypothesis is that increased fluid flow from increased capillary filtration might produce streaming potentials, a possible signal for increased cellular activity.