Uncontrollable hemorrhage accounts for a large proportion of total mortality in both civilian (31%) and military (47%) trauma victims. Hypothermia is a relatively safe method that could provide total body protection during hypovolemic shock and facilitate surgical intervention as a potentially life-saving procedure. This study tested the hypothesis that profound hypothermia and complete blood replacement in an established canine model, would facilitate resuscitative therapy from exsanguinating hypovolemic shock. Adult dogs were prepared for extracorporeal bypass using closed-chest peripheral cannulation under general anesthesia. Controlled hypotensive, hemorrhagic shock (mean arterial blood pressure < 50 mmHg) was induced for 30 min at normal temperature followed by temporary resuscitation using crystalloid infusion for approximately 10 min. Using our established procedure, the dogs were then cooled externally to 27 degrees C before initiating blood substitution with Hypothermosol (Cryomedical Sciences, Inc. Rockville, MD) via the extracorporeal pump. The heart was arrested during further cooling to below 10 degrees C and Hypothermosol was recirculated for 2 hr, with (3 dogs) or without (5 dogs) 1 hr of circulatory arrest. During rewarming the animals were autotransfused, weaned from the pump, and allowed to recover. All dogs (n = 8) survived, all but one with complete neurologic recovery: blood chemistry samples examined immediately after the procedure showed significant differences (p < 0.05) in only a few parameters, including creatine kinase (CK-BB and CK-MB), compared with the previous group of control dogs. The consistent survival of dogs showing apparently normal neurologic, physiologic, and biochemical recovery supports the concept that profound hypothermia using a protective hypothermic blood substitute could provide time for therapeutic resuscitation of currently intractable trauma cases.