A high fasting respiratory quotient (RQ) was observed during the treatment by very low calorie diet (VLCD) in obese patients who regained weight at two-year follow-up (weight regainers) or in those who exhibited repeated cycles of weight loss with a subsequent weight regain (weight cyclers). In contrast obese patients who succeeded to retain the weight loss achieved initially by the VLCD at 2-yr follow-up (weight losers) or those who did not exhibit weight fluctuations (weight noncyclers) were characterized by a significantly lower RQ. Therefore a high fasting RQ during the VLCD treatment should be considered predictive of body weight gain. Resting metabolic rate (RMR) expressed per kg fat free mass (FFM) did not influence body weight changes. A high RQ revealed in obese subjects reporting parental obesity and a low fasting RQ observed in those obese without family history of obesity suggest a role of hereditary factors in the ability to oxidize fat in severely obese subjects. In contrast, parental history of obesity did not affect RMR in severely obese individuals.