This study explored time-frequency analysis of surface electrocardiograms in patients with persistent atrial fibrillation for monitoring atrial drug action. Drug loading over 3 days with oral flecainide (n = 13) or amiodarone (n = 17) organized the fibrillatory process expressed by decreased atrial fibrillatory rate, increased rate stability, and decreased exponential decay. Effects were more pronounced with flecainide than with amiodarone.