Eight obese and eight lean women were studied in a metabolic unit for up to 4 weeks to assess the thermogenic response to fat overfeeding. An extra 4.3 MJ fat were given to both obese and lean groups for 6 days after a preliminary weight-maintenance diet. The fat overfeeding was repeated following a period of semistarvation. The obese women initially had a higher 4-h expenditure (9.9 +/- 1.1 MJ) than the lean (7.4 +/- 0.6 MJ). Fat overfeeding induced a variable increase in energy output (340 +/- 197 kJ in the obese and 612 +/- 147 kJ in the lean) amounting to 7.8 +/- 4.5 percent of the supplement's energy in the obese and 14.2 +/- 3.4 percent in the lean. The response to the fat supplement during semistarvation remained low in the obese at 3.6 +/- 4.9 percent but fell substantially in the lean (8.1 +/- 3.8 percent). These results suggest that there is a flexibility in the normal thermogenic response to fat in lean subjects but a reduced response in those with familial obesity.