Parabiosis of obese (ob/ob) with diabetes (db ^2J/db^2J) mice caused the obese partner to become hypoglycemic, to lose weight and to die of starvation, while no abnormal changes were observed in the diabetes partner. The striking similarity of this response to that observed in normal mice in parabiosis with diabetes mice suggests that obese mice are like normal mice in having normal satiety centers sensitive to the satiety factor produced by the diabetes partner. In contrast, parabiosis of obese with normal mice is a fully viable combination suggesting that the obese partner does not produce sufficient satiety factor to turn off the normal partner's eating drive. However, obese mice in parabiosis with normal mice gain weight less rapidly and eat less than obese mice in parabiosis with obese mice. These observations suggest that some humoral factor is provided by the normal partner that regulates food consumption in the obese partner. To explain the identical obese-hyperglycemic syndromes produced by these two unrelated and separate genes when on identical genetic backgrounds, it is postulated that the obese mouse is unable to produce sufficient satiety factor to regulate its food consumption, whereas the diabetes mouse produces satiety factor, but cannot respond to it because of a defective satiety center.