Controversy exists presently as to whether thyroid hormone potentiates the action of catecholamines on the heart. Therefore, the relationships between adrenergic sensitivity, myocardial beta-receptor number, and the cardiovascular responses associated with excess thyroid hormone were investigated in pigs (Sus scrofa). A hyperthyroid state was induced by the administration of triiodothyronine (T3; 1 mg/kg iv). After 7 days there was a significant increase in resting heart rate, systolic blood pressure, rate-pressure product, and O2 consumption in the hyperthyroid state. At this time echocardiography showed a substantial increase in myocardial cross-sectional size. Pharmacological tests showed an increased intrinsic heart rate (127 +/- 29 to 205 +/- 25 beats/min; P less than 0.001) and an increased chronotropic sensitivity to isoproterenol. The concentration of isoproterenol required for a 50% of maximal response (ED50) was reduced by 33 +/- 30% (2.1 +/- 1.0 to 1.2 +/- 0.3 micrograms/l; P less than 0.025). The slope of the line relating isoproterenol concentration and change in heart rate was increased by 29 +/- 33% (61 +/- 10 to 78 +/- 10; P less than 0.025). Radioligand studies demonstrated an increase in the number of beta-receptors in right atrial membranes from hyperthyroid animals (41 +/- 7 vs. 75 +/- 18 fmol/mg; P less than 0.02). The apparent dissociation constant (KD) of the receptor for l-isoproterenol was similar in membranes from euthyroid and hyperthyroid animals (157 +/- 57 vs. 219 +/- 59 nM, respectively; P = NS). This study demonstrates that hyperthyroidism is associated with an increased chronotropic sensitivity to isoproterenol, consequent to an up-regulation of beta-adrenergic receptors in the right atrium.