The relationship between the sympathetic nervous system and cardiovascular responses has been studied indirectly in ten hyperthyroid patients and age matched euthyroid controls. Nyctohemeral variations in heart rate, and heart rate and blood pressure responses to exercise were measured before and during beta-blockade with slow-release propranolol. Both groups showed a parallel variation in heart rate over 24 h, with an increase in heart rate inthe hyperthyroid group that was the same during the day (27.9 +/- 0.95 beats/min) and during the night (26.7 +/- 0.75 beats/min). Similarly, the increase in resting heart rate (32.7 +/- 4.4 beats/min) in the hyperthyroid group was close to the increase in peak exercise-induced heart rate (25.0 +/- 4.7 beats/min). Adequate beta-blockade was achieved in all subjects as evidenced by a percentage reduction in peak exercise heart rate of 25-45%. Propranolol caused a greater reduction in daytime than night-time heart rate in both groups and blunted the response to exercise. Following beta-blockade, the mean percentage reduction in heart rate and systolic blood pressure during exercise, and heart rate responses over 24 h were similar in hyperthyroid and euthyroid groups. The closest correlation between thyroid hormone levels and heart rate was that of serum total tri-iodothyronine (T3) and nocturnal heart rate during beta-blockade (r=0.92; P less than 0.0001). It is concluded that excess circulating thyroid hormones exert a direct effect on the cardiovascular system additive to the sympathetic nervous system and that there is no evidence of adrenergic hypersensitivity in hyperthyroidism.