Rodents tend to compensate for experimental obesity, in which both adipocyte size and number are increased. In contrast, it was recently reported that Siberian hamsters do not compensate for dorsal subcutaneous transplants of fat, which increase body fat without changing the size of adipocytes. In the first experiment described here we tested whether mice changed the size of their endogenous fat stores 2 or 5 weeks after donor fat was added as subcutaneous transplants. Each epididymal fat pad from donor mice was cut in half and placed ventrally in recipient mice, increasing body fat by approximately 10%. After two weeks there was no effect of the transplants on the size of endogenous fat depots or the size of adipocytes in epididymal fat depots. There was a substantial decrease in mass and adipocyte size in transplanted fat. Five weeks after surgery the endogenous epididymal and retroperitoneal fat depots of recipient mice were significantly decreased, serum leptin was reduced and the size of adipocytes in endogenous epididymal fat was significantly reduced, although cell number had not changed. The size of transplanted cells was the same as at two weeks. In a second experiment epididymal fat was placed as either dorsal or ventral subcutaneous fat transplants. Five weeks after surgery the endogenous fat depots were decreased in all recipient mice but none of the differences reached statistical significance. These results suggest that mice have mechanisms to maintain total body fat mass that respond to an increase in the number of fat cells present.