Abnormal repolarization associated with torsades de pointes is expressed as QT prolongation. The physiological response to class Ia antiarrhythmic drugs is also reflected in prolongation of the QT interval. However, the essential difference between pathological and physiological prolongation is not clear. The purpose of this investigation was to differentiate between pathological and physiological changes in the repolarization waves of surface electrocardiograms (ECG) induced by class Ia drugs. In 18 patients without a history of torsades de pointes or syncope (control group), TU waves were compared before and after the administration of class Ia drugs (physiological response). In eight patients with torsades de pointes induced by class Ia drugs (torsades de pointes group), the TU waves at torsades de pointes were compared with those before drug administration (pathological response). In the control group, although the QTc (measured in lead II and corrected for heart rate by Bazett's formula) was increased significantly (0.40 +/- 0.04 to 0.44 +/- 0.05 s, P < 0.001), the U-amp (amplitude of the U wave measured in a precordial lead where the T and U waves were clearly differentiated) remained unchanged. In the torsades de pointes group, however, the QTc was increased (0.42 +/- 0.04 to 0.54 +/- 0.07 s, P < 0.02); the U-amp was also increased, significantly (0.09 +/- 0.07 to 0.27 +/- 0.18 mV, P < 0.05). Thus, enlargement of the U wave may help to differentiate between the physiological and pathological responses to class Ia drugs.