Temporary cessation of blood flow is a necessary aid for certain complex neurosurgical and cardiovascular procedures, and hypothermia is often used to help protect against the deleterious effects of ischemia and anoxia. In an attempt to protect cellular integrity during ultraprofound hypothermia (< 10 degrees C) and complete blood substitution, two new crystalloid-colloid blood substitutes (Hypothermosol-maintenance [HTS-M] and Hypothermosol-purge [HTS-P]) have been evaluated. Using extracorporeal bypass, 14 dogs were totally exsanguinated during cooling using the HTS-P solution, then perfused (40-85 ml/kg/min; mean arterial blood pressure = 25-40 mmHg) with either TS-M (Group I, n = 11), or with HTS-P as controls (Group II, n = 3) for 3 hr at 7 degrees C. During warming, the dogs were autotransfused and observed neurologically and biochemically during recovery. All dogs in Group I recovered and eight have survived long term (12-80 weeks) without apparent neurologic deficits. In contrast, dogs in Group II were more difficult to revive (cardiac resuscitation); two survived long term with delayed neurologic recovery. Evaluation of biochemical parameters showed only a transient and inconsequential elevation in enzymes (e.g., brain, liver, and heart) in Group I compared with the markedly greater elevations in Group II. The faster neurologic recovery of dogs treated with the "intracellular" maintenance solution supports the biochemical data showing the benefits of this type of blood substitute for extending the safe limits of hypothermic cardiac arrest to beyond 3 hr.