We have evaluated a five-compartment model of 18Ffluoride kinetics in rats. The initial fluoride distribution was found to be similar to that of 77Brbromide, a known extracellular-fluid (ECF) tracer, in agreement with the hypothesis underlying the model, and the measured uptake rate in rat bones compared well with the digital computer solution. Simpler models did not give a better fit. In dead rats, fluoride movement was found within the skeleton, presumably from bone ECF to bone substance, although not as rapidly as predicted or found in the live animal. Evaluation of the rate constants permitted estimates to be made of cardiac output, skeletal blood flow, and bone ECF volume, all in accord with independent measurements. It is suggested that skeletal blood flow at rest is a constant fraction of body weight, and probably subserves a hematopoietic as well as a mineralization function.