Depletion and structural interactions between dilute, large, nearly hard-sphere colloidal particles in a fluid dispersion containing much smaller nearly hard spheres were investigated as a function of small-particle concentration in sedimentation experiments. It shows that low concentrations of fine particles can destabilize larger particles due to the attractive depletion forces, while at higher concentrations of small particles, the surface-induced structural forces prevent large-size particles from approaching each other and thereby stabilize the large-particle suspension. A theoretical model based on the Ornstein–Zernike method was used to calculate the interparticle interactions in a bidis-persed colloidal system in which small particles are polydispersed. The theoretical re-sults explain the experimental observations.