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A compensation for differences in bone material quality by bone geometric properties in femora from two different strains of rats was previously shown by us. A feedback mechanism controlling the mechanical properties of the integrated bones was then proposed, in accordance with Frost's mechanostat theory. Evidence of such a system is now offered by the finding of a negative correlation between the modeling-dependent cross-sectional architecture (moment of inertia) and the mineral-dependent stiffness (elastic modulus) of bone material in the femoral diaphyses of 45 normal Wistar rats of different sexes, ages, and sizes. The strength and stiffness of the integrated diaphyses were found to depend on both cross-sectional inertia and body weight, not on bone mineral density. These findings are interpreted as supporting the hypothesis that the architectural efficiency of diaphyseal cross-sectional design resulting from the spatial orientation of bone modeling during growth is optimized as a function of the body weight-dependent bone strain history, within the constraints imposed by bone stiffness. Results suggest a modulating role of biomass, related to the system set point determination, and explain the usually observed lack of a direct correlation between mineral density and strength or stiffness of long bones in studies of geometrically inhomogeneous populations.