This study was performed to determine the cardiac electrophysiological effects of cocaine and specifically to determine the time course of these actions. Eighteen chronically instrumented conscious dogs were tested with i.v. cocaine at doses of 1 or 4 mg/kg. The following statistically significant changes were observed 1 min following the 4 mg/kg dose of cocaine: heart rate increased from 135 +/- 8 to 186 +/- 9 beats/min, QRS duration increased from 60 +/- 5 to 74 +/- 5 ms, corrected QT interval increased from 298 +/- 7 to 339 +/- 8 ms, intraatrial conduction time increased from 27 +/- 2 to 31 +/- 3 ms, atrioventricular conduction time increased from 125 +/- 5 to 140 +/- 8 ms, and the atrial effective refractory period (ERP) increased from 101 +/- 6 to 130 +/- 9 ms. All of these parameters had returned to baseline by 10 min after cocaine administration. Corrected sinus node recovery time and the ventricular ERPs were not significantly affected by either cocaine dose. The only significant change produced by the 1 mg/kg cocaine dose was prolongation of the atrial ERP. These results suggest that cocaine causes very transient electrophysiological changes that undoubtedly represent the integrated effects of the adrenergic and local anesthetic actions of this drug.