The effects of interfacial adhesion strength on the mechanical behavior of composites of polyamide 66 and precipitated calcium carbonate (CaCO3) particles have been investigated. The 50 nm average diameter particles have been surface-treated using two kinds of coupling agent having various affinities with respect to the matrix. The surface-modified particles have been incorporated into the polyamide matrix via melt processing. Tensile and impact tests, associated with dynamical mechanical analysis, have been performed on injection-molded samples. The structural characterization of the specimens has been carried out using differential scanning calorimetry and wide-angle X-ray scattering. It is observed that the matrix structure is roughly insensitive to the surface treatment, despite a weak nucleating effect of the filler particles. In contrast, the particle surface treatment strongly influences the particle dispersion in the polymer matrix. Although dispersion was not optimized, the elastic properties of the reinforced polyamide increase with the CaCO3 content, below as well as above the glass transition temperature. Impact toughness decreases for CaCO3 weight fraction greater than 5%. Scanning electron microscopy investigation reveals that the interfacial adhesion affects local deformation processes, such as debonding and fibrillation of the polymer matrix around the particles, during the macroscopic deformation of the composites.