The mean density of fat-free mass (FFM) is remarkably stable at 1.10 g/cm(3) in healthy adult humans, and this stability is a cornerstone of the widely applied densitometry-based two-compartment model for estimating total body fat. At present, the usual means of exploring FFM density is by in vitro or in vivo experimental studies. The purpose of the present investigation was to develop a cellular-level body composition model that includes seven factors that determine FFM density. The model, when applied with available empirical coefficients, predicted an FFM density similar to that observed in vivo. An analysis of the seven model components indicates that the ratio of extracellular solids to total body water is a major determinant of individual variation in FFM density. The difference in FFM density across sex, race, and age groups was examined with the developed model. The present study thus provides a conceptual framework for the systematic study of FFM density in humans.