A chemical approach to establishing human body density in vivo was developed by combining recently developed noninvasive methods. Four compartments were measured: protein (P; prompt-gamma neutron activation), water (A; 3H2O dilution), mineral (M; dual-photon absorptiometry and delayed-gamma neutron activation), and fat (F; dual-photon absorptiometry). By this model body weight is equal to P + A + M + F. This approach was applied to 13 healthy adults (8 females and 5 males). The four compartments accounted for greater than 97% actual body weight. Calculated density based upon composition agreed within 0.6 +/- 0.4% (mean +/- SD) with density (D) measured by hydrodensitometry [calculated D (g/cc) = 0.86 measured D +0.15; r = 0.94, p less than 0.001]. The average calculated lean (P + A + M) density of 1.096 +/- 0.007 g/cc agreed closely with three classic human cadaver studies (1.100 g/cc). This multicompartment approach provides a new opportunity to estimate human body density in vivo and to refine body composition methods based upon an assumed but inadequately validated constant lean density.