In 65 consecutive surgical patients with multinodular goitre and with preclinical hyperthyroidism (TRH-resistant suppression of TSH in the presence of normal circulating thyroid hormones) the individual values of the FT4-index (FT4-I) and FT3-index (FT3-I) showed a wide range form low normal to high normal with mean values not differing from those in TRH\x=req-\ responsive goitre patients and from controls. Thirty-five patients underwent repeated pre-operative TRH tests: 11 (group A) were TRH-unresponsive on one occasion, and TRH-responsive at another time. Fifteen (group B) were TRH-unresponsive on two occasions. Nine patients (group C) were preclinically hyperthyroid on one occasion and had supranormal individual thyroid hormone concentrations at another time. In multinodular goitre patients with preclinical hyperthyroidism a significant T3 increase was observed after oral TRH. In spite of a TRH-resistant suppressoin of TSH small amounts of TSH are thus still secreted. The degree of TSH suppression may be the result of a varying degree and pattern of continued, fluctuating or elapsed increase in thyroid hormone supply. The T3 response to oral TRH depends not only on the degree of TSH suppression, but also subtlely on the thyroidal reserve: in euthyroid TRH-TSH negative goitre patients a decrease of the TSH-regulated follicular mass by goitre resection abolished the pre-operatively significant T3 response to TRH during the post-operative phase of transient TSH deficiency.Preclinical hyperthyroidism was defined as TRHresistant suppression of TSH in the presence of circulating thyroid hormone concentrations in the normal range ). In multinodular goitre patients this functional state of euthyroid TRH unresponsiveness was attributed to a degree of autonomous thyroid hormone secre¬ tion by parts of the goitrous tissue (Gemsenjäger et al. 1976; Miller 1980; Studer et al. 1978b) which was slightly supranormal and sufficient to suppress the TSH response to TRH, but insufficient to produce continuous hyperthyroidism. Following surgical ablation of autonomously thyroid hor¬ mone secreting tissue TRH responsiveness re¬ covered (Gemsenjäger et al. 1976; Blichert-Toft et al. 1978). The present study gives evidence -1. that, on the base of repeated measurements of thyrotrophic and thyroid function, preclinical hyperthyroidism is a graded condition with a vary¬ ing thyroid hormone supply, -2. that TSH may not be suppressed completely in patients with pre¬ clinical hperthyroidism, as demonstrated by the T3 responsiveness to TRH, -3. that the T3 response to TRH in subjects with an absent TSH response to TRH depends not only on the various degree of TSH suppression but also on the thyroidal respon¬ siveness. Patients and Methods Definitions TRH unresponsiveness. Absence of detectable serum TSH 30 min after iv and 3 h after oral TRH, respectively, i.e. a serum TSH value of < 1 mU/1 after TRH. Preclinical hyperthyroidism. TRH-resistant suppression of TSH in the presence of circulating thyroid hormone concentrations in the normal ra...