['Factors that influence energy metabolism and substrate oxidation, such as thyroid hormones (THs), may be important regulators of body weight.', 'We investigated associations of THs cross-sectionally with obesity, energy expenditure, and substrate oxidation and prospectively with weight change.', 'Euthyroid, nondiabetic, healthy, adult Pima Indians (n = 89; 47 M, 42 F) were studied. Percentage body fat (%BF) was measured by using dual-energy X-ray absorptiometry; sleeping metabolic rate (SMR), respiratory quotient, and substrate oxidation rates were measured in a respiratory chamber. Thyroid-stimulating hormone (TSH), free thyroxine (T(4)), free triiodothyronine (T(3)), and leptin concentrations were measured in fasting plasma samples.', 'TSH, but neither free T(3) nor free T(4), was associated with %BF and leptin concentrations (r = 0.27 and 0.29, respectively; both: P <or= 0.01). In multiple regression analyses adjusted for age, sex, fat mass, and fat-free mass, free T(3) was a positive predictor of SMR (P = 0.02). After adjustment for age, sex, %BF, and energy balance, free T(3) was a negative predictor of 24-h respiratory quotient (P < 0.05) and a positive predictor of 24-h lipid oxidation rate (P = 0.006). Prospectively, after an average follow-up of 4 +/- 2 y, the mean increase in weight was 3 +/- 9 kg. Baseline T(3) concentrations were associated with absolute and annual percentage of changes in weight (r = -0.27, P = 0.02, and r = -0.28, P = 0.009, for the age- and sex-adjusted associations, respectively).'] Do plasma concentrations of free triiodothyronine predict weight change in euthyroid persons?