Thyroidal concentrations of T4 and T3 and the T4/T3 ratio were analyzed in the nodular and paranodular tissues from two groups of patients with suppressed TSH secretion. The first group consisted of 17 patients with nontoxic nodular goitre (NG), 8 of whom received long-term levothyroxine therapy to suppress TSH, while remaining 9 were untreated. The second group consisted of 10 patients with autonomously functioning thyroid adenoma (AFTA), in whom TSH secretion was suppressed due to the adenoma-induced increase in thyroid hormone concentrations. In nodular tissues of NG patients, thyroidal T4 and the T4/T3 ratio were significantly higher in treated than in untreated patients (0.34 +/- 0.05 vs. 0.15 +/- 0.02 mol T4/mol of thyroglobulin (Tg) and 10.9 +/- 1.2 vs. 5.2 +/- 0.7 respectively). Analysis of paranodular tissues of NG patients also revealed a higher T4/T3 ratio in treated patients (16.0 +/- 2.1 vs. 6.9 +/- 0.9), although thyroidal T3 and T4 concentrations in treated and untreated patients were similar. In AFTA patients, both T3 and T4 concentrations were higher in the adenoma than in paranodular tissues (0.14 +/- 0.04 vs. 0.02 +/- 0.005 mol T3/mol Tg and 1.08 +/- 0.32 vs. 0.26 +/- 0.06 mol T4/mol Tg), whereas the T4/T3 ratio was significantly higher in paranodular tissues (23.2 +/- 5.9 vs. 9.3 +/- 1.8). These results indicate that suppression of TSH induced either exogenously or endogenously results in an increase in the thyroidal T4/T3 ratio that reflects an increase in T4 and/or a decrease in T3 concentrations. These findings also support the notion that TSH preferentially stimulates thyroidal T3 production.