SUMMARY: Determinations of the total serum tri-iodothyronine (T3) and total serum thyroxine (T4) were performed in healthy persons, and in patients with various thyroid diseases. In addition, tracer doses of 131I-labelled T3 and 125I-labelled T4 were given intravenously, and the disappearance rates of each hormone were plotted graphically. From this single injection slope-intercept technique, the volumes of distribution, half-times, fractional rates of disappearance, and hormonal production rates were calculated by standard techniques. In normal persons, the average T3 production was 44·75 μg daily, and that for T4 97·30 μg/day. In most hyperthyroid patients, the production of both hormones was increased in equal proportions to the normal group. In four patients with 'T3-thyrotoxicosis', the total serum T4 and T4 production rates were within normal limits, and only T3 production was increased. In patients with primary hypothyroidism, the production of both hormones was reduced: however, T4 production was more markedly reduced than T3 production. Two patients with Hashimoto's disease who were clinically euthyroid showed low T4 production rates, but T3 production was almost within normal limits. These findings suggest that in primary thyroid deficiency there appears to be a sequential failure of T4 production and then of T3 production, before hypothyroidism develops clinically. This may be due to increased endogenous thyrotrophin, and perhaps a low intrathyroidal iodine content. In contrast, patients with secondary hypothyroidism due to hypopituitarism had much higher ratios of T4:T3 production rates than patients with primary hypothyroidism.