The effects of changing body size, energy intake and substrate oxidation on serum T4, FT4, T3, FT3 and TSH were investigated in ten morbidly obese subjects (4 men/6 women; age: 37 +/- 6 years; BMI: 53.8 +/- 6.5 kg/m2; mean +/- SD) who had undergone a surgical bilio-pancreatic by-pass in order to reduce their body weight. The starting value of serum FT3 was inversely related to the BMI (r = -0.63; p < 0.05). After 1-3 months, all the subjects were losing weight and their intake of carbohydrates was almost negligible; at this time a significant reduction of T3 (-14.6%; p < 0.0001), T4 (-19.5%; p < 0.0001), and FT3 (-10.5%; p < 0.001) was observed. Nine to 16 months after surgery, all the subjects were still losing weight, although there was no carbohydrate restriction; T3, T4, and FT3 were lower than prior to surgery but were beginning to increase. Finally, after 36-42 months the body weight of all the patients had been stable for at least the previous six months (final BMI: 32.9 +/- 4.1) and their body composition, as assessed by bio-impedance, was almost normal; only the concentrations of FT3 proved to be significantly lower than the basal value (-11.2%; p < 0.03). The change in FT3 proved to be independently influenced by the degree of fat malabsorption but not by changes in any of the physical characteristics considered. All values were always in the normal range; FT4 and TSH did not change significantly during the whole period of study. The final concentrations of TSH proved to be independently related to the postabsorptive protein oxidation (g/24h) (TSH = 2.37-0.018* protein oxidation). These results would suggest that nutritional factors have some influence on the blood levels of thyroid hormones, especially of FT3, while the removal of obesity does not seem to have any independent effect in the long-run.