OBJECTIVE The combined effects of limited food intake and OE treatment have been analysed in order to determine whether hypocaloric diets enhance the slimming effects of OE on mature overweight male rats. Two levels of dietary limitation at 50 and 25% of a standard intake were established, roughly corresponding to the human LCDs and VLCDs. METHODS Wistar male rats (6 weeks old) were made overweight by a cafeteria diet. After transition to standard diet, they were subjected to food restriction: down to 50 or 25% with respect to the transition period. Half the animals were given daily oral gavages of 10 nmol/g oleoyl-estrone (OE), and the rest received only the vehicle during 10 days. METHODS Changes in weight and body composition: water, lipid, protein or gross energy were determined by comparing the final pool size with that of day 0, calculated from the initial body weight and the composition of untreated rats. Energy and nitrogen balances were estimated. Plasma levels of metabolites and hormones were also measured. RESULTS OE induced changes in body composition similar to those elicited by a 50% reduction in food, with massive loss of lipid and energy. OE-treated rats ate less than the controls, but additional effects on body composition on reduced diet were minimal. OE improved metabolic homoeostasis: better maintained glycaemia, lower cholesterol and shallower hormonal changes, but at the expense of slightly increased protein mobilisation. CONCLUSIONS The data presented suggest that no advantages are accomplished by combining OE treatment and hypocaloric diets compared with OE alone, at least under the experimental conditions tested, since the effects were not additive. Despite OE affecting food intake, mechanisms other than that are deemed responsible for the mobilisation of body fat, since intake alone cannot explain the effects on body weight, nor the metabolic and hormonal changes in OE-treated rats. It is concluded that the combination of food restriction and OE may result in unwanted increased protein mobilisation with no synergy between both slimming treatments.