The kinetics of 99mTc(Sn) methylene diphosphonate [99mTc(Sn)MDP] were evaluated by means of compartmental analysis in 5 normal children and 17 thalassemic subjects. Blood and urine activity were analyzed with a computer program which generates intercompartmental rate constants by an iterative least-square method providing a best-fit to the input data. The amount of tracer in each compartment (corrected for decay) was determined as a function of time. The transfer rate of 99mTc(Sn)MDP from blood to extracellular fluid and lamellar bone (K1-3) was about 20% higher in thalassemic subjects than in normal children. The transfer rate of 99mTc(Sn)MDP from blood to woven bone (K1-4) was about 57% higher in thalassemic subjects. A faster rate of spread into woven bone appears to be the major cause of higher bone uptake of 99mTc(Sn)MDP in thalassemic subjects, which suggests that in these patients bone tissue reoccupies the space previously replaced by hyperplastic marrow. Moreover, the increased bone extraction rate revealed a correlation between anemia and bone metabolic activity.