BACKGROUND: Heart rate variability is a sensitive marker of cardiac sympathetic activity. OBJECTIVES: To determine whether long-term hyperthyroidism induced by thyroxine suppressive therapy affects HRV. METHODS: Nineteen patients treated with suppressive doses of thyroxin for thyroid cancer and 19 age-matched controls were enrolled. Thyroid function tests and 1 minute HRV were performed on all subjects and the results were compared between the groups. The 1 minute HRV was analyzed during deep breathing and defined as the difference in beats/minute between the shortest and the longest heart rate interval measured by eletrocardiographic recording during six cycles of deep breathing. RESULTS: One minute HRV during deep breathing was significantly lower among thyroxine-treated patients compared to healthy controls (25.6 +/- 10.5 vs. 34.3 +/- 12.6 beats/min, P < 0.05). There were no significant differences in mean, maximal and minimal heart rate between the groups. CONCLUSIONS: Thyroxine therapy administered for epithelial thyroid cancer resulted in subclinical hyperthyroidism and significantly decreased HRV due to autonomic dysfunction rather than basic elevated heart rate.