Deuterium oxide (D(,2)O) dilution was evaluated for use in estimating body composition of ruminants. Empty body composition of cattle could not be accurately estimated by two- or three-compartment models when solved on the basis of clearance of D(,2)O from blood. Multiple compartmental models were not useful in detecting a 47% increase in rumen volume that was induced by feeding cattle a high roughage diet as opposed to feeding a high grain diet. Application of regression equations with compartmental modeling did not improve prediction of body composition because of variation between different populations of animals. A one-compartment model, in which a regression equation was used to estimate the water in the contents of the gastrointestinal tract, was useful in estimating relative differences in body composition between animals, but was not accurate in estimating the exact value of composition;A 29-compartment blood-flow model was developed from measured blood flow rates and water volumes of tissues of sheep. The rates of equilibration of water in tissues that were simulated by the blood-flow model were much faster than actual rates measured in sheep and cattle. The incorporation of diffusion hindrances for movement of water into tissues enabled the blood flow model to simulate the measured equilibration rates in tissues, but the values of the diffusion coefficients were different for each tissue. The D(,2)O-disappearance curve for blood simulated by the blood-flow model with diffusion limitations was comprised of four exponential components. The disappearance of D(,2)O from blood measured in sheep did not reflect the equilibration process that occurred in tissues, which seemingly is the reason compartmental models do not accurately predict the quality of water in portions of the body of ruminants;The tissues and gastrointestinal tract contents were placed into five groups based upon the rate of equilibration. Water in the organs of the body equilibrated with water in blood within 3 min. Water in visceral fat, head, and some of the gastrointestinal tract tissues equilibrated within 8 to 16 min. Water in skeletal muscle, fat, and bone and the contents of some segments of the gastrointestinal tract equilibrated within 30 to 36 min. Water in the tissues and contents of the cecum and upper-large intestine equilibrated within 160 to 200 min. Water in ruminal tissue and contents equilibrated within 480 min.