In a previous study occlusion of a middle cerebral artery (MCA) followed by 48 h of hypothermia (29°) was lethal in 5 of 5 monkeys as compared to only 3 of 9 normothermic animals. The present study extended these observations in monkeys and cats with or without MCA occlusion. In monkeys MCA occlusion plus 48 h of hypothermia was consistently lethal. Without MCA occlusion 2 of 3 monkeys survived, but were comatose the first 12 h post-hypothermia. In normothermic cats, MCA occlusion was lethal in only one of 5 animals whereas hypothermia was lethal in 20 of 21 cats with or without MCA occlusion. The detrimental effects of hypothermia were not favorably influenced either by hemodilution or by deliberate alterations in PacOj. The effect of 48 h of hypothermia and rewarming on cerebral blood flow (CBF) and cerebral metabolites was evaluated in 6 normal monkeys. CBF was reduced 60 to 70 percent at 29°C and returned to only a maximum of 50 percent of control with re-warming. Prior to re-warming distribution of CBF was inhomogeneous. Cerebral metabolites were borderline normal prior to re-warming but energy stores decreased while lactate increased with re-warming.