Marked changes in cardiac function have been noted in patients with hyperthyroidism or hypothyroidism due both to changes in sympathetic system function and to biochemical modifications of myocardial tissue. Metaiodobenzylguanidine (MIBG), an analogue of norepinephrine, can be used to evaluate myocardial sympathetic tone. Here, we report myocardial 123I-MIBG kinetics in patients with differentiated thyroid carcinoma undergoing acute hypothyroidism followed by hormonal replacement as part of their routine clinical follow-up. Ten patients with differentiated thyroid carcinoma in acute hypothyroidism (A) and on hormonal replacement with thyroxine (150 micrograms.day-1) and triiodothyronine (20 micrograms.day-1) (B) underwent scintigraphic imaging 20 min and 4 h after injection of 111 MBq of ultra-high specific activity 123I-MIBG. No patient had cardiac disease or was taking medications that could interfere with cardiac or autonomic system function. Cardiac MIBG kinetics (heart-to-mediastinum, H/M, ratio and myocardial washout rate), serum norepinephrine, T3, T4, FT3, FT4, TSH, CPK, CPK-MB, blood pressure and ECG were evaluated. Systolic and diastolic blood pressure did not differ significantly between state A and state B. In the acute hypothyroid state (A), the prevalence of non-specific ST-T abnormalities was 70% and heart rate was significantly different (P < 0.001) than in state B. Norepinephrine and CPK-MB levels were higher during hypothyroidism, but this did not reach statistical significance. A positive correlation between early H/M and delayed H/M in the hypothyroid state (r = 0.57) and an even higher positive correlation between early H/M and delayed H/M in the euthyroid state (r = 0.91) were seen. The myocardial and mediastinal MIBG washout rates were significantly different between the hypothyroid and euthyroid states (P < 0.05), whereas the lung washout rate did not differ significantly between the two metabolic states. We conclude that the myocardial washout rate during hypothyroidism is clearly increased (P < 0.005) with a subclinical derangement of myocardial adrenergic innervation, which is rapidly reversed with hormonal therapy.