The right/left ratios of tibial uptake of 99(m)Tc diphosphonate (EHDP) and relative blood flow (based on microsphere distribution) were determined in control rats and rats with a ligated right femoral artery or a healing right tibial fracture. Correlation between 99(m)Tc EHDP uptake and relative blood flow was highly significant (r = 0.917; P<0.0001) for relative flow ratios less than 1.7. When the ratio was greater than 1.7, there was little further increase in 99(m)Tc EHDP uptake. Ligation of the femoral artery in rats with healing fractures resulted in a more marked reduction of blood flow than of 99(m)Tc EHDP uptake. These results suggest that regional bone blood flow is a major determinant of 99(m)Tc EHDP uptake, though changes in regional tracer extraction efficiency are also important.