This study investigates the effects of gross loss of body weight on glucose disposal (GD), storage (GS), oxidation (GO), and the thermogenic response (TR) during hyperinsulinemic euglycemic glucose infusion in 9 underweight but nourished patients (UP) and in 3 of the patients after weight gain (WGP). In UP, baseline metabolic rate (MR) was 4.1 ± 0.2 kJ/min and respiratory exchange ratio (RER) 0.97 ± 0.02. During the final 30 minutes of hyperinsulinemia MR rose by 0.32 ± 0.07 kJ/min (p<.01) and RER rose to 1.09 ± 0.03 (p<.01). GD was 61 ± 3 μmol/kg per minute, GO 35 ± 1 μmol/ kg per minute, and GS 26 ± 4 μmol/kg per minute. The energy cost of glucose storage as glycogen was 0.15 kJ/min, and as lipid was 0.2 kJ/min. In WGP baseline MR was 4.5 ± 0.4 kJ/ min and RER was 0.91 ± 0.03. During hyperinsulinemia MR rose by 0.63 ± 0.2 kJ/min, RER rose to 0.93 ± 0.02, GD was 53 ± 4 μmol/kg per minute, GO was 30 ± 3 μmol/kg per minute, and GS was 23 ± 1 μmol/kg per minute. The energy cost for this glucose storage was 0.22 kJ/min.Therefore, during hyperinsulinemia in UP, GD, and TR are similar, but GO is greater and GS is less than previously reported in healthy subjects. However, this TR is entirely accounted for by the energy cost of glucose storage with no evidence of facultative thermogenesis. In WGP, all responses were similar to those in healthy subjects, and the TR was in excess of that required of the energy cost of glucose storage. (Journal of Parenteral and Enteral Nutrition16:5–10, 1992)