In a double-blind trial physiological doses (60 microgram/day) of triiodothyronine (T3) were compared with placebo in a group of obese patients on a 320 kcal/day (1.34 MJ) liquid formula diet. T3-treated patients had a significantly greater weight-loss by the 12th week. Analysis of serum levels of T3 and thyroxine (T4) showed that those patients in the placebo group whose weight-loss tended to level off at a plateau towards the end of the trial also had the lowest T3 levels and resting metabolic rate (RMR) at that time. Patients in the T3 group had a steady rise in serum T3 levels during the 12 wk period. Those with the highest final T3 levels had the greatest tendency for their weight-loss to level out and, paradoxically, had the least suppression of serum T4 levels and lowest RMR. Some obese patients who do not readily lose weight on conventional low-calorie diets may have an impaired metabolic clearance rate of T3 and a degree of T3 resistance.