In two patients with variant forms of Brugada electrocardiographic abnormalities, ST segment elevation, and reciprocal ST segment depression developed during intravenous administration of pilsicainide. In one patient, pilsicainide accentuated the ST segment elevation in leads I, aVL, and V1-V3 and caused ST segment depression in leads II, III, and aVF. Coronary angiograms at the time of ST segment elevation were normal. In the other patient, pilsicainide accentuated the coved-type ST segment elevation in leads II, III, and aVF and caused ST segment depression in leads I, aVL, and V2-V5. Frequent premature ventricular complexes (PVCs) with two different left bundle branch block patterns developed during ST segment elevation. Intravenous isoproterenol returned the ST segment to baseline in both patients and suppressed the PVCs in the second patient. We hypothesize that a wide area of epicardial myocardium with large Ito current might explain the reciprocal ST segment depression observed at the time of accentuated ST segment elevation.