The acute effects of amiodarone (AM), a potent antiarrhythmic drug, on tetrodotoxin (TTX)-sensitive component of action potentials of Purkinje fibers from guinea pig were studied by use of conventional microelectrode techniques, and compared the findings with the results obtained in the papillary muscle. 2. The present study showed that the action potentials of Purkinje fibers (PF) were more sensitive to AM, compared to those of papillary muscle. 3. Acute exposure (30 min) to 4.4 x 10(-5) M AM led to a depression of plateau potential of PF action potential, but the drug did not affect the total action potential duration. 4. TTX (2-4 x 10(-6) M) shortened the PF action potential duration at all levels of repolarization. 5. The depression of PF plateau potential in the presence of AM was, at least in part, involved in a decrease in TTX-sensitive plateau sodium current, because no further depression of the plateau potential was observed by addition of TTX in the presence of AM.