The thermic effect of food has been observed to be decreased in subgroups of obese nondiabetic and obese diabetic subjects. The mechanisms responsible for this decrease have not been fully elucidated. Although protein elicits the largest thermic effect among the various nutrients, most studies have addressed carbohydrate- or fat-induced thermogenesis in insulin resistance. To determine whether the decreased thermic effect of nutrients in insulin-resistant patients could be related to a decrease in protein-induced thermogenesis, glucose [13.9 mumol.kg fat-free mass (FFM)-1.min-1] with or without amino acids (4.2 mg.kg FFM-1.min-1) was infused into a group of six obese nondiabetic subjects (Ob), six obese subjects with non-insulin-dependent diabetes mellitus (NIDDM), and six lean subjects. The thermic effect of infused amino acid (% of infused energy) measured by indirect calorimetry was 21.1 +/- 3.2%, 23.8 +/- 1.8%, and 20.0 +/- 2.9% in lean, Ob, and NIDDM subjects, respectively (NS). It is concluded that the thermic effect of protein is not altered in insulin-resistant patients.