Objectives: To evaluate energy balance after three isocaloric oral loads of different composition and to establish possible relationships between the substrates oxidative patterns and the modifications of insulin and free fatty acids (FFA) plasma profiles. Design: Each subject received, in a randomized order, three oral loads of 2658 +/- 45 kJ (636 +/- 11 Kcal) either as glucose, lipids (cream) or a mixture (glucose + cream). Setting: The experiments were performed at the University Hospital of Geneva. Subjects: Ten normal body-weight volunteers. Methods: Energy expenditure GEE) and substrates oxidation were measured by indirect calorimetry during 8 h following each load. Plasma glucose, insulin and FFA were also measured. Results: EE was 1776 +/- 107, 1818 +/- 125 and 1785 +/- 117 KJ over 8 h after glucose, mixed and lipids load, respectively. Glucose oxidation was the highest after oral glucose as compared to mixed and lipids load, while the highest value of lipids oxidation was measured after fat load. A significant relationship Linked fat oxidation to plasma FFA (r= 0.54, P < 0.002) as well as to insulin (r = - 0.40, P < 0.002). Conclusions: (a) The energetic cost of glucose and fat intake is the same; (2) after each load, the main source of energy corresponds to the substrate administered; (3) both plasma insulin and FFA influence the substrate oxidative patterns observed after each load; (4) alimentary fat may contribute to fat oxidation by maintaining elevated plasma FFA levels.