Thyroglobulin (Tg) was obtained by fine needle aspiration from patients with untreated hyperthyroidism due to Graves' disease and untreated hypothyroidism to determine whether alterations in its T4 and T3 content could account for the disproportionately high serum T3 compared to serum T4 found in both diseases. For comparison aspiration was performed from normal thyroid tissue in euthyroid patients operated for solitary thyroid lesions. The average amounts of Tg aspirated were: normal 177 +/- 52 (SE) micrograms, n = 7, hyperthyroidism 82 +/- 32 micrograms (n = 8); hypothyroidism 4.6 +/- 1.9 micrograms, n = 9. The iodothyronine content of Tg was, normal, T4 3.7 +/- 0.5 mol/mol, T3 0.28 +/- 0.04 mol/mol, T4/T3 13.7 +/- 1.4; hyperthyroidism, T4 3.8 +/- 1.0, T3 0.59 +/- 0.15, T4/T3 6.8 +/- 1.1; hypothyroidism, T4 3.3 +/- 0.5, T3 0.54 +/- 0.09, T4/T3 6.8 +/- 0.7. The iodine content of Tg was 28 +/- 3.1 atoms/mol in the euthyroid subjects and 31 +/- 7.3 atoms/mol in hyperthyroid patients. Hence, both untreated hyperthyroidism and untreated hypothyroidism were characterized by Tg with a normal T4 but a relatively high T3 content. This is probably related to the prolonged hyperstimulation of functioning follicular cells present in both diseases. The relatively high T3 content of Tg could not alone explain the relatively high T3 production compared to T4 production in these two thyroid diseases.