Opioid antagonism and serotonergic stimulation is associated with macronutrient-specific hypophagia in animals. In the present study we evaluated their systemic effect alone, and in combination, at various doses, on the intake of sweet carbohydrate-rich and sweet fat-rich foods, tastes, and nutrients that are typical of binge-food items. Low-dose (1 mg/kg) naloxone, alone, preferentially suppressed fat-rich intake while low-dose (2.5 mg/kg) fluoxetine, alone, preferentially suppressed carbohydrate-rich intake. Each drug at these doses, combined with various doses of the other (2.5-10 mg/kg fluoxetine; 0.01-1 mg/kg naloxone) additively suppressed both kinds of the sweet foods. Naloxone and fluoxetine have therapeutic potential in treating binge eating disorders. This animal study suggests what shortcomings and benefits might be expected when combining these two agents.