1. Sixteen adult male volunteers were selected on the basis of body size and customary food intake: half could be described as 'lean' and habitually consuming large amounts of food (group mean +SEM: 15.03k 1.13 MJ/d), the high-energy-intake group (HE1 group), and half though 'lean' admitted to a weight problem and regularly consumed a lower than average food intake (group mean ~S E M :6.90k0.39 MJ/d), the low-energy-intake group (LEI group).2. Energy expenditure was measured by open-circuit indirect calorimetry. Resting metabolic rate (RMR) was recorded. A meal (Complan, either 2.1 MJ or 4.2 MJ), ephedrine hydrochloride (0.25 mg and 0.50 mg/kg body-weight) or a water control were then administered and metabolic rate (MR) was measured for 4 h. Blood was collected before and 1 h after the meal or drug, and the serum analysed for various hormones and blood metabolites.3. The size of the thermic response to feeding but not the time-course was related to meal size in both groups. MR increased by 21.6 and 28.6% in the HE1 group and by 8.2 and 20.0% in the LEI group in response to the 2.1 and 4.2 MJ Complan meals respectively. Fasting insulin levels were similar in both groups but showed a significantly higher level in the LEI than HE1 group after the Complan meals.4. The mean RMR increased by 5.2 and 10.3% in the LEI in response to ephedrine and by 15.7 and 11.2% in the HE1 groups after 0.25 mg and 0.50 mg ephedrine/kg respectively. The rise in serum-free fatty acids in response to ephedrine was significantly higher in the HE1 group than in the LEI group.5. These results suggest (1) the meal size required to promote a maximum thermic effect is smaller in energeticallyinefficient individuals (2) the sensitivity to a sympathomimetic drug is also increased in energetically-inefficient individuals.6. We conclude that in energetically-efficient individuals both the thermic response to a meal and the sympathetic-mediated thermogenesis are lower than in energetically-inefficient ones.In recent years, there has been considerable interest in the mechanisms involved in maintaining energy balance. In particular, the possibility that the regulation of energy expenditure may be fundamental to the control of body-weight has been investigated in both animal and human studies. Thus, the ability to increase energy expenditure after prolonged overfeeding of carbohydrate in man (Sims et al. 1973) or of cafeteria diets in rats (Rothwell & Stock, 1979) has been well documented. This facultative thermogenesis involves an increase in the resting metabolic rate (RMR) and may be mediated through sympathetic stimulation of brown adipose tissue metabolism and other thermogenic pathways in much the same way as cold-mediated thennogenesis.A second component of diet-related thermogenesis is the extra heat production associated with each individual meal, the thermic effect of feeding (TEF), which may lead to a 1040% increase in RMR after feeding (Bray, 1970; Miller, 1976). Although reports are conflicting, a critical evaluation of the evidence (G...