Patients with persistent atrial fibrillation (AF) who respond to ibutilide infusion usually convert to sinus rhythm within 1 hour. However, little is known about the magnitude and time course of the drug's atrial electrophysiological effects. In the current study, the frequency content of the fibrillatory baseline on the ECG was used to quantify the effects of ibutilide infusion on AF. Nineteen patients (age 56 +/- 16 years) in persistent AF were studied. Nine of these were chronically treated with antiarrhythmic drugs. All subjects received ibutilide (1 mg i.v.) over 10 minutes and a second dose 10 minutes later as needed. An ECG was recorded and digitized throughout each of the 20 sessions (one patient had two separate cardioversions). A signal processing technique was then used to quantify the average rate of the fibrillatory baseline. After attenuating the QRS and T waves, the ECG was subjected to Fourier transformation. The average rate of fibrillatory activity was defined as the frequency corresponding to the peak power of this spectrum. The fibrillation rate declined by 20 +/- 12% during the initial dose of ibutilide. This effect was rapid with t1/2 = 4.2 minutes. Ibutilide induced slowing of AF was more intense and more rapid in patients who converted to sinus rhythm than in those who did not (25 +/- 5% vs 18 +/- 14% drop in rate, t1/2 3.4 minutes vs 6.3 minutes, P = 0.002). Ibutilide induced slowing of fibrillatory activity occurs rapidly and approaches steady state before the end of a 10-minute infusion. Although interaction with other antiarrhythmic drugs may have confounded the results, the speed and intensity of slowing correlated with conversion. These observations suggest that additional studies are warranted to determine if ibutilide dosing regiments can be optimized.