The roles of β-adrenoceptor were well known in hyperthyroidal heart, but not with α-adrenoceptor. So we studied the effects of phenylephrine on membrane potential, intracellular sodium activity (aⁱ_Na), twitch force, and intracellular pH (pH_i) by continuous intracellular recordings with ion-selective and conventional microelectrodes in the papillary muscles of hyperthyroid guinea pig heart. α₁-Adrenoceptor stimulation by phenylephrine (10^-5 or 3 × 10^-5M) produced the following changes: variable changes in action potential duration, a hyperpolarization (1.5 ± 0.1mM) of the diastolic membrane potential, an increase in aⁱ_Na (0.4 ± 0.15mM), a stronger positive inotropic effect (220 ± 15%), an increase in pH_i (0.06 ± 0.002 unit). These changes were flocked by prazosin and atenolol. This indicated that the changes in membrane potential, aⁱ_Na twitch force, and pH_i are mediated by a stimulation of the α₁-Adrenoceptor. Ethylisopropylamiloride (10^-5) also blocked the increase in aⁱ_Na and twitch force. On the other hand, strophanthidin, tetrodotoxin, Cs⁺ or verapamil did not block the increase in aⁱ_Na and twitch force. Thus, it was suggested that α₁-Adrenoceptor stimulation increased aⁱ_Na and pH_i by stimulation of Na⁺-H⁺ exchange, thereby allowing intracellular alkalinization and aⁱ_Na increase. These results were very different from euthyroidal heart which showed α₁-Adrenoceptor-induced decrease in aⁱ_Na and initial negative inotropic effect. From the above results, it was concluded that α₁-Adrenoceptor had a important role in hyperthy-roidal heart.