Nutrient selection emerges as a result of both genetic and environmental factors and may be further modified by stressors. The impact of this complex interrelationship on pathological outcomes is poorly understood. In the present investigation the stressor-reactive BALB/cByJ and the relatively stressor resilient C57BL/6ByJ mice were maintained on a macronutrient selection protocol or given free access to chow for 20 months. The C57BL/6ByJ mice exhibited a marked preference for fat over carbohydrates, whereas BALB/cByJ mice preferred carbohydrates over fat. Cognitive testing in a Morris water maze indicated that while BALB/cByJ mice were clearly more impaired in this task relative to their C57BL/6ByJ counterparts, there was no substantial effect of the diet at either 13 or 19 months of age. Furthermore, despite their stressor resiliency, at 19 months of age, C57BL/6ByJ mice who invariably consumed fat, exhibited greater plasma corticosterone responses to a 20-min period of restraint than chow fed animals. Indeed, the corticosterone rise was as pronounced as in the more reactive BALB/cByJ strain. Furthermore, the C57BL/6ByJ diet-fed mice showed features of insulin insensitivity and increased adiposity. These data suggest that the adverse effects of fat consumption need to be considered in the context of genetically determined vulnerability/resilience factors.