Recent evidence has shown that mice deficient in the NPY Y2 receptor have an increase in trabecular bone volume as well as cortical bone mass due to increased osteoblast activity. However, the mechanical phenotype of Y2 -/- bone has not yet been assessed. Thus, the aim of the present study was to examine the effect of Y2 deletion on murine cortical bone structural behavior, as well as to assess the material and geometric contributions to that behavior. The results of this study indicate that Y2 -/- mice on a 129 SV x Balb/c background strain are smaller in body mass and have smaller bones than wild-type controls. As expected based on smaller bone cross-sectional properties, cortical bone structural strength was lower in -/- animals. Surprisingly, the structural stiffness of -/- bones was comparable to that of +/+ bones despite their smaller cross-sectional geometry. Comparable structural stiffness appeared to be achieved by means of an elevated effective shear modulus, which was associated with a small, but statistically significant, higher ash content in Y2 -/- bones. These data represent the first comprehensive characterization of the effect of Y2 deletion on cortical bone structural and material behavior to date.