In order to evaluate the efficacy of a TSH supressive dose of levothyroxine to reduce the volume of a single thyroid nodule we studied 55 euthyroid patient: 45 (group A) were suppressed with LT(4) (mean 1.7+/-0.9 mu g/Kg/day) for 21.3+/-5.3 months, and 10 patients (group B) served as controls. All the nodules were ''cold'' at scintiscanning, solid at ultrasonography and benign by fine-needle aspiration cytology. As responders were assumed the nodules shrinked at the end of treatment of 50% in volume. Thyroid function values (TSH, T-4, FT4, T-3, FT3, thyroid peroxidase and thyroglobulin antibodies), clinical and ultrasonographic findings were evaluated initially and at the end of the study. A significant nodular volume decrease occurred in 8 treated patients (17.8%) while 37 (82.2%) amongst the group suppressed and all controls showed no change (A vs B=NS). In two untreated patients new nodules were noted; no new nodules were discovered in the treated group (A vs B p<005). No side effects occurred in any treated patient, even if at the end of treatment a significant T-4 and FT4 (p<0.01) increase was observed, No one onset parameter can predict the response to the therapy. These results suggest that only a small group of patients affected by a single thyroid nodule seems to respond to a TSH suppressive therapy.