The passage of tissue fluid through cortical bone has been investigated using radioactively labelled macromolecules as markers. The results suggest that in the cortex of young rabbit femur the movement of tissue fluid is in the same net direction as blood, mainly from the endosteal to the periosteal surface. Some albumin is incorporated from extravascular tissue fluid into calcified matrix at sites of bone formation. Polyvinylpyrrolidone, average molecular weight 35,000, is able to pass through extravascular tissue fluid in bone but is not incorporated into calcified matrix. In rabbits made vitamin D deficient, much less alblmin is retained in regions of bone formation than is the case with controls. Albumin adsorbs to the surface of calcium phosphate precipitates and it is suggested that this mechanism may be mainly responsible for its incorporation into bone.