In cold-water drowning, attempts at restoration of spontaneous circulation (ROSC) by external cardiopulmonary resuscitation (CPR) often fail. We explored the longest period of asphyxial cardiac arrest from cold-water submersion (without inhalation of water) from which ROSC is possible using cardiopulmonary bypass (CPB). In 19 lightly anesthetized dogs the tracheal tube was clamped (simulating laryngospasm) and the dogs were immersed in ice water from 20, 40, 60, 90, or 120 minutes. Cardiac arrest occurred after six to 11 minutes of submersion. At start of resuscitation, rectal temperature ranged from 21 C (after 60 minutes) to 34 C (after 20 minutes of submersion), and cerebral temperature was between 7 C (after 120 minutes) and 27 C (after 20 minutes submersion). Resuscitation attempts were performed according to protocol in 16 dogs, using only CPB by venoarterial pumping with an oxygenator and a heat exchanger. Priming was with 400 to 800 mL Dextran 40 and Ringer's solution 1:1 plus heparin. CPB flows were 10 mL/kg/min, and they increased to achieve normotension and return of rectal temperature to 32 C. After one-half to three hours, of CPB, ROSC was successful in 75%. This percentage included one of three dogs after 90 minutes submersion, but not in the one dog after 120 minutes submersion. Spontaneous breathing and EEG activity returned in 56% at two to 24 hours, after 20 to 90 minutes of submersion. Failure of ROSC attempts apparently were due to clotting in large vessels during arrest and capillary leakage during reperfusion. CPB is effective for ROSC after prolonged hypothermic cardiac arrest, and it should be evaluated in animal outcome studies.