We sought to develop a model of cardiac arrest and resuscitation on mice that would be comparable to that of large mammals and would allow for more fundamental investigations on cardiopulmonary arrest and cardiac resuscitation. A model of cardiopulmonary resuscitation previously developed by our group on rats was adapted to anesthetized, mechanically ventilated adult male Institute of Cancer Research mice that weighed 46 ± 3 g. The trachea was intubated through the mouth, and end-tidal PCO₂ (PET_CO2) was measured with a microcapnometer. 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 or a pulseless rhythm. Precordial compression was begun 4 min later. Ten sequential studies were performed, during which five animals were successfully resuscitated and five failed resuscitation efforts. Successful resuscitation was contingent on the restoration of threshold levels of CPP and PET_CO2 during chest compression. As in rats, swine, and human patients, threshold levels of mean aortic pressure, CPP, and PET_CO2 were critical determinates of resuscitability in this murine model of threshold level of cardiac arrest and resuscitation.