Fluid flow that arises from the functional loading of bone tissue has been proposed to be a critical regulator of skeletal mass and morphology. To test this hypothesis, the bone adaptive response to a physiological fluid stimulus, driven by low magnitude, high frequency oscillations of intramedullary pressure (ImP), were examined, in which fluid pressures were achieved without deforming the bone tissue. The ulnae of adult turkeys were functionally isolated via transverse epiphyseal osteotomies, and the adaptive response to four weeks of disuse (n=5) was compared to disuse plus 10 min per day of a physiological sinusoidal fluid pressure signal (60 mmHg, 20 Hz). Disuse alone resulted in significant bone loss (5.7±1.9%, p⩽0.05), achieved by thinning the cortex via endosteal resorption and an increase in intracortical porosity. By also subjecting bone to oscillatory fluid flow, a significant increase in bone mass at the mid-diaphysis (18.3±7.6%, p<0.05), was achieved by both periosteal and endosteal new bone formation. The spatial distribution of the transcortical fluid pressure gradients (∇Pr), a parameter closely related to fluid velocity and fluid shear stress, was quantified in 12 equal sectors across a section at the mid-diaphyses. A strong correlation was found between the ∇Pr and total new bone formation (r=0.75, p=0.01);​ and an inverse correlation (r=−0.75, p=0.01) observed between ∇Pr and the area of increased intracortical porosity, indicating that fluid flow signals were necessary to maintain bone mass and/or inhibit bone loss against the challenge of disuse. By generating this fluid flow in the absence of matrix strain, these data suggest that anabolic fluid movement plays a regulatory role in the modeling and remodeling process. While ImP increases uniformly in the marrow cavity, the distinct parameters of fluid flow vary substantially due to the geometry and ultrastructure of bone, which ultimately defines the spatial non-uniformity of the adaptive process.