To examine the effect of chronic endogenous melanocortin receptor (MC-R) antagonism on macronutrient diet selection, A^y/a mice that ectopically overexpress the MC-R antagonist, agouti, were fed a three-choice macronutrient diet of pure fat, carbohydrate, and protein. A^y/a mice gained more weight and consumed a greater proportion of their daily intake from fat and less from carbohydrate than wild-type littermates did. The increased fat preference was present immediately, and persisted throughout the 7-week long experiment. Protein intake was greater for A^y/a mice; however, the proportion of protein intake to total intake was similar between mouse types. Ovarian fat pads of A^y/a mice comprised a greater percentage of total body weight that that from wild-type littermates. These results suggest that endogenous inhibition of MC-Rs mediate the increased fat intake in growing mice.