To determine whether or not the weight (and fat) loss induced by oleoyl-oestrone treatment results only as a consequence of decreased food intake, we compared treated animals with a pair-fed model. To this end, Wistar female rats received daily oral gavages of 10μmol/kg per d oleoyl-oestrone in sunflower oil, or vehicle alone for 10 or 20d. A second group of rats received the gavage of sunflower oil and the same amount of food ingested as the oleoyl-oestrone-treated animals (pair-fed group). Rats treated with oleoyl-oestrone maintained glucidic metabolism homeostasis despite a marked decrease in adipose tissue weight (P<0·001). Pair-fed rats exhibited a different pattern, comparable to short-term starvation, with greatly decreased glycogen stores (P<0·0001). The most significant effects were detected in the 10d period groups. Oleoyl-oestrone affected the activity of the ponderostat system not only by decreasing appetite but also by modifying energy partition: treated animals maintained their glucose and energy homeostasis despite decreased food intake and the massive depletion of lipid stores.