The effect of hyperthyroidism on cardiac sensitivity to beta-adrenergic stimulation in humans is controversial. To determine whether heart rate and left ventricular contractile sensitivity to beta-adrenergic stimulation are altered by hyperthyroidism in human subjects, the frequency, velocity and extent of left ventricular shortening at rest and during a 4-stage graded dose isoproterenol infusion were characterized in eight young healthy subjects before and after 2 weeks of daily administration of 100 micrograms of triiodothyronine (T3). The rate and extent of left ventricular shortening were determined by Doppler and two-dimensionally guided M-mode echocardiography. In the hyperthyroid state, heart rate at rest was faster (57 +/- 3 vs. 68 +/- 4 beats/min; p less than 0.001) and the slope of the relation of heart rate to the rate of isoproterenol infusion was 36% steeper (1,538 +/- 126 vs. 1,131 +/- 95; p less than 0.05). The left ventricular ejection time was shorter and the mean velocity of left ventricular circumferential fiber shortening (mVcf) was greater during all stages of isoproterenol infusion in the hyperthyroid versus the euthyroid state (p less than 0.01). After adjustment for the faster heart rate after T3 administration, left ventricular ejection time and mVcf were similar in the euthyroid and hyperthyroid states at baseline and during maximal beta-adrenergic stimulation but shortened and enhanced, respectively, during stages 1 and 2 of isoproterenol infusion (p less than 0.05). There was no effect of T3 administration on left ventricular mass, dimensions, end-systolic wall stress or stroke volume at rest or during any stage of isoproterenol infusion. These results indicate that in human subjects hyperthyroidism of short duration increases the sensitivity of heart rate and left ventricular shortening velocity to beta-adrenergic stimulation in the absence of changes in left ventricular mass, loading conditions or extent of shortening.