Transcranial doppler measurements of blood flow velocity in the middle cerebral artery were made during treatment of raised intracranial pressure (ICP) in 22 patients with severe brain injury. Twenty patients also had continuous measurement of arterial and jugular bulb venous oxygen saturation (SJO2). The transcranial Doppler parameters studied included both mean flow velocity and pulsatility index (PI). Successful treatment was defined as a reduction of ICP to less than 20 mm Hg with improvement or preservation of cerebral perfusion pressure (CPP) above 60 mm Hg. Successful therapy was associated with a significant rise in SJO2 and reduction of cerebral arteriovenous oxygen content difference (AVDO2) and PI only when the pretreatment CPP was less than 60 mm Hg. An increase in CPP beyond 70 mm Hg did not further improve cerebral oxygen delivery and PI, suggesting that autoregulation became a factor above this CPP threshold. Treatment failure during administration of hypnotic drugs resulted in a reduction in arterial pressure, CPP, SJO2, and mean velocity and in an increase in PI and AVDO2, despite a decrease in ICP. CPP is the most important parameter to monitor during ICP therapy. It should be maintained above 70 mm Hg in patients with severe brain injury.