Chronic prophylactic hyperventilation therapy should be avoided during the first 5 days after severe TBI and particularly during the first 24 h. CBF measurements in patients with severe TBI demonstrate that blood flow early after injury is low and strongly suggest that in the first few hours after injury the absolute values approach those consistent with ischemia. These findings are corroborated by AVdO2 and SjO2 and brain tissue O2 measurements. Hyperventilation will reduce CBF values even further, but will not consistently cause a reduction of ICP and may cause loss of autoregulation. The cerebral vascular response to hypocapnia is reduced in those with the most severe injuries (subdural hematomas and diffuse contusions), and there is substantial local variability in perfusion. While the CBF level at which irreversible ischemia occurs has not been clearly established, ischemic cell change has been demonstrated in 90% of those who die following TBI, and there is PET evidence that such damage is likely to occur when CBF drops below 15-20 cc/100 g/min. A prospective randomized clinical trial has determined that outcomes are worse when TBI patients are treated with chronic prophylactic hyperventilation therapy. Within the standard, guideline, and options, specific paCO2 thresholds have been described that are different for each of the three parameters. These individual thresholds were selected based on the preponderance of literature supporting those thresholds in the contexts of the statements which included them. With the exception of the threshold included for the standard in this guideline, it is emphasized that the paCO2 threshold is not as important as the general concept of hyperventilation. The preponderance of the physiologic literature concludes that hyperventilation during the first few days following severe traumatic brain injury, whatever the threshold, is potentially deleterious in that it can promote cerebral ischemia.