The relationship between size of a mixed, liquid meal and the thermic effect of food (TEF) was studied in two groups of nonobese male subjects differing in maximum serobic capacity (VO2 max). A design using repeated measures was chosen in which each subject received each meal (water, 500 kcal, 1000 kcal, 1500 kcal) on a different morning. TEF was measured by indirect calorimetry for three hours following each meal and was found to increase systematically, in a nonlinear fashion, as meal size was increased. Subjects with a high VO2 max responded to the two higher calorie meals with a greater TEF than did subjects with a low VO2 max. They also showed a greater increase in TEF for any given increase in meal size. This study establishes a precise relationship between meal size and the thermic effect of food. It also identifies an important variable, VO2 max, in determination of the individual thermic response to food. These findings suggest that individuals with a high VO2 max (such as aerobically trained athletes) show a greater caloric expenditure after eating, particularly after a large meal, than do individuals with a low VO2 max. A high thermic response to food could be beneficial in body weight homeostasis. © 1984.