Thermic effect of food (TEF) studies give conflicting answers to research questions and in many cases data from one laboratory to another is not comparable because of the utilization of different experimental methods. Likewise, how weight reduction affects measurement of TEF is controversial. Two studies were conducted on how TEF affects energy expenditure. The first study examined how resting energy expenditure (REE) measurements can affect TEF studies and how much within-subject variation is found in TEF studies. The TEF of a standard meal was measured in six subjects for 6.5 h on three different occasions by indirect calorimetry. REE was measured on each subject for 1 h before the meal was given on each measurement occasion. On a separate day, the energy expenditure was measured on each subject during the same time period as the TEF measurement, but without any food given to determine if a circadian increase in REE over the time period of the measurement was observed. We found no circadian increase in energy expenditure during the 6.5 h of the REE study. While the within-subject variation in REE (four measurements) had an average coefficient of variation of 5.2% (range 2.4-8.5%), the coefficient of variation of the TEF measured (three measurements) was 26.4% (range 13.6-50.9). In the second study, REF and the TEF were measured before and after weight reduction in moderately overweight adult women. Nine women weighing between 62.1 and 84.7 kg lost an average of 7.3 kg while on a reduced calorie, low fat diet for between 12 and 14 weeks. After weight reduction, the average REE of these subjects decreased by 8.8% or 515 kJ (123 kcal)/24 h. The TEF of these nine women was measured for 6.5 h before and after weight reduction using 16 oz of Sustacal, 2008 kJ (480 kcal). Before weight reduction the thermic effect of Sustacal was 264 kJ (63 kcal) or 13% of calories consumed, and after weight reduction it was 251 kJ (60 kcal) or 12.5% of calories consumed. We did not find the TEF to be lower than expected in these subjects before weight reduction, since TEF is often reported to be around 10% of energy consumed, and it was not changed after weight reduction.