The effect of a low-calorie diet (200 kcal) composed of about 50 per cent glucose and 50 per cent protein on body weight, thyroid hormone levels and pituitary thyrotrophin response was studied in 18 grossly obese subjects (relative weight 131-205 per cent) for 28 d; during the last 14 d eight subjects (Gp B) served as controls, while in the other ten subjects (Gp A) the low T3-high rT3 state was treated by T3 supplementation (150 micrograms daily). During the first 14 d (period 1) weight loss (corrected for the sodium diuresis) appeared to be constant and to be equal for both groups. The thyroid hormone concentration and the basal and TRH stimulated TSH concentrations were similar to the results from previous total starvation studies. Despite marked changes in serum T3 levels a normal pituitary TSH response was maintained and no delayed response of TSH to TRH occurred. During T3 supplementation the serum T3 levels increased to high values, the rT3 concentration declined to below initial values, the T4 and TSH concentrations were depressed and the response of the TSH concentration to TRH disappeared; apparently these 'high normal' levels of serum T3 must be considered inappropriate for this condition of severe calorie restriction. In the controls the serum T3 levels remained constant after the end of the first period; the serum rT3 concentration declined from day 14 to day 28, but remained above the initial values. The serum T4 concentration remained almost constant during the whole study; basal and TRH stimulated TSH concentrations did not change during the whole study. During period 2 weight loss diminished in the control group, but remained constant in Gp A (T3 supplemented); the correlation between the weight loss and the increase of the serum T3 concentration during triiodothyronine supplementation was significantly negative (r = -0.64; P less than 0.05). The well-being of the subjects did not change during T3 administration and no signs of hyperthyroidism developed. One could speculate this reflects a decrease in number or sensitivity of intracellular receptor sites. It is concluded that at the peripheral level no complete resistance develops against T3 administration; in the low T3 state the hypothalamic-pituitary axis reacts as if euthyroidism exists.