The mechanism(s) underlying preference for individual macronutrients (particularly fat) in diet are poorly understood. The greatest obstacle in designing experiments to define neurochemical determinants of fat preference lies in our ability to clearly identify animals' macronutrient preference (MP) profile. To this end, we have defined the role of several variables and suggested ways to design better studies to examine the mechanism of macronutrient preference. The results of these studies show that the paradigm used for MP analysis, genetics and age of the animal could clearly affect the MP profile.