While screening outbred male Holtzman Sprague-Dawley rats for their macronutrient (protein, carbohydrate, and fat) preferences, we noticed substantial group-to-group variation in the preference profile. This led us to analyze preference data on two hundred and seventy rats collected over a three-year period to determine whether preferences could be predicted. The results led us to conclude that observed variations in macronutrient preference profiles may be secondary to genetic heterogeneity in the outbred population. We have also shown that the outcome of the pharmacologic effects of two agents (insulin and enterostatin) on appetitive behavior will vary from animal to animal within a single group. Accordingly, researchers must be aware that the breeding history of the laboratory animal is a major factor in the outcome of the experiment and interpretation of the findings.