The purpose of this study was to evaluate the use of retrograde cerebral perfusion via the superior vena cava during profound hypothermia and circulatory arrest (CA) in pigs. In three groups of 5 pigs each, group A (control) underwent cardiopulmonary bypass and normothermic CA for 1 hour, group B underwent cardiopulmonary bypass, profound hypothermia, and CA (15 degrees C nasopharyngeal) for 1 hour, and group C underwent the same procedure as group B plus retrograde cerebral perfusion. In group A none awoke. In group B, 2 of 5 did not awake and 3 of 5 awoke unable to stand, 2 with perceptive hind limb movement and 1 moving all extremities. In group C all awoke, 4 of 5 able to stand and 1 of 5 unable to stand but moving all limbs. In neurologic evaluation group B had significantly lower Tarlov scores than group C (p = 0.0090). Group B mean wake-up time, plus or minus standard error of the mean, was 124.6 +/- 4.6 minutes versus 29.2 +/- 5.1 in group C (p = 0.0090). In group B late phase CA cerebral blood flow dropped 30.9% +/- 4.8%, but in group C it rose 24.7% +/- 9.3% (p = 0.0007, pooled variance t test, two-tailed). In group B late phase CA brain oxygenation decreased 46.0% +/- 13.9% but it increased 26.1% +/- 5.4% in group C (p = 0.0013). This difference was reduced somewhat during rewarming (B, -21.2% +/- 14.9%; C, 16.4% +/- 4.7%; p = 0.043). Group B rewarming jugular venous O2 saturation was 30.8% +/- 2.5% versus 56.0% +/- 4.4% in group C (p = 0.0011). We conclude that in pigs retrograde cerebral perfusion combined with profound hypothermia during CA significantly reduces neurologic dysfunction, providing superior brain protection.