While significant attention has been devoted to the identification of hormonal factors that control body mass, little attention has been paid to the role of mechanical loading on animal mass. Here, we provide evidence that intraperitoneal implantation of metabolically inert mass results in a compensatory reduction in tissue mass. Deer mice (Peromyscus maniculatus) were surgically implanted with weights of 1, 2 or 3 g. There was a resulting loss of tissue mass (total body mass minus implant mass) that was proportional to the mass of the implant. This reduction in tissue mass followed a reduction in food intake in animals with 3 g implants. Evaluation of body composition failed to identify any single component that contributed to the loss of tissue mass. Removal of implants led to a transient restoration of body mass to levels similar to the total body mass of those control animals in which the implant had not been removed. However, within 12 days of implant removal, body mass again declined to the level seen before implant removal. These results suggest the existence of a set point that is sensitive to changes in the perception of mass and that is transduced via neural pathways.