Background. We sought to develop a model of cardiac arrest and resuscitation on mice which would be comparable to that of large mammals and which would allow for more fundamental investigations on cardiopulmonary arrest and cardiac resuscitation. Methods. A model of CPR previously developed by our group on rats has been adapted to anesthetized, mechanically ventilated adult male ICR mice weighing 46±3 g. The trachea was intubated through the mouth and end-tidal CO₂ (P_ETCO₂) was measured with a micro-capnometer. Catheters were advanced into the aorta and into the right atrium, and coronary perfusion pressure (CPP) was computed. A 1.5 mA alternating current was delivered to the right ventricular endocardium which produced ventricular fibrillation (VF) or a pulseless rhythm. Precordial compression was begun 4 minutes later. Results. Ten sequential studies were performed during which 5 animals were successfully resuscitated and 5 failed resuscitation efforts. Successful resuscitation was contingent on the restoration of threshold levels of CPP and P_ETCO₂ during chest compression. Conclusion. As in rats, swine and human patients, threshold level of mean aortic pressure, CPP, and P_ETCO₂ were critical determinates of resuscitability in this murine model of cardiac arrest and resuscitation.