This paper reviews the literature on the role of dietary fat in calorie intake and body weight gain in humans and laboratory animals. An overview of 40 animal studies which compared growth on high-fat (HF) and high-carbohydrate (HC) solid/powdered diets indicated that the HF diet elicited greater weight gain in 33 out of 40 studies. Enhanced growth on the HF diet was often, but not exclusively, attributable to greater caloric intake. Additional evidence for the growth-enhancing effect of HF diets emerges from "diet option" and "supermarket" feeding studies in rats, and experimental and epidemiological studies in humans. Three principal factors that contribute to the different responses to HF and HC diets are (a) caloric density, (b) sensory properties and palatability, and (c) postabsorptive processing. It is concluded that both calorie intake and metabolic energy expenditure are biased towards weight gain when a HF diet is consumed, and that the high caloric density of high-fat diets plays a primary role in weight gain. Humans may be biologically predisposed to gain weight when a HF diet is consumed.