When one member of a parabiosed pair of rats is overfed, its ad libitum-fed partner loses body fat in the absence of a statistically significant decrease in food intake. Three experiments investigated the relationships between food intake, metabolism, and body composition in this model. In vivo measurement of lipogenesis confirmed that loss of fat is associated with decreased fat deposition. When partners of overfed rats were compared with food-restricted single rats, proportional changes in body composition and metabolism were similar for the two treatments, although there was no significant change in the food intake of parabiotic rats, whereas restricted rats received only 60% of the intake of their controls. The final experiment demonstrated that changes in body composition of partners of overfed rats were independent of dietary composition. These results suggest that, when a rat is made obese by overfeeding, a circulatory factor is released that inhibits fat deposition and disrupts regulatory mechanisms that normally stimulate food intake during a period of negative energy balance.