BACKGROUND: Clinically apparent thyroid nodule is a very common disease in adults. Patients are often treated with thyroxine in order to reduce the size of the nodule, but the efficacy of thyroxine-suppressive therapy with thyroxine remains uncertain. We investigated the efficacy of thyroxine-suppressive therapy and the hormonal characteristics during thyroxine therapy to find out whether such measurement could be used to determine the effectiveness of this therapy in patients with benign solitary thyroid nodule proved by aspiration biopsy. METHODS: In this study, 54 patients were randomly assigned to receive L-thyroxine (Group I, n=24) or placebo (GroupII, n=30) for 1 year. High resolution ultrasonography (10MHz) was used to measure the size of the nodules at six month intervals. Thyroid hormones and thyroglobulin assay and FNA (fine needle aspiration) was done at the same time. The dose of thyroxine was 200ug/day. Patients were followed at 6 month intervals. RESULTS: The results were as follows: 1) 13 (54.1%) out of 24 Group I patients after adequate TSH suppression had a statistically significant reduction of nodule size and before-to-after nodule volume ratios were significantly different between the Group I and Group II patients. 2) In the responders among Group I patients, the before-to-after therapy ratio of the nodule volume was not related to the pretreatment nodule size, thyroid hormones and thyroglobulin levels. CONCLUSION: Thus we concluded that an adequate suppressive dose of L-thyroxine significantly altered the volume of the benign solitary thyroid nodules 12 months later.