BACKGROUND AND PURPOSE: Guinea pigs are used as models for study of ventricular tachyarrhythmias (VT); however, the tachyarrhythmia often is transient and does not persist. We developed an open-thorax guinea pig model of sustained ventricular fibrillation (VF). METHODS: Bilateral thoracotomy was performed on eight guinea pigs weighing 865 to 1,464 g, and two sutures were positioned in the right ventricular apex for the purpose of pacing. Two methods were used to induce VF: a 50-Hz burst (normal pacing), and an initial 15 beats at 70% of the R-R interval followed by a 100-Hz burst for 84 beats (rapid pacing). Fifteen attempts at inducing VF were performed by use of each method. Blood pressure was recorded before and after development of VF, which was defined as VT with mean blood pressure consistently <10 mm Hg. A final observation was obtained using the normal pacing method without defibrillation. RESULTS: Use of both methods successfully induced VF. A significant relationship between body weight >1,021 g and ability to sustain and survive VF was detected. CONCLUSION: The guinea pig is a useful rodent model for the study of VF and defibrillation.