Middle cerebral artery blood flow velocity and jugular bulb venous oxygen saturation (SJO2) were measured by transcranial Doppler (TCD) ultrasonography and continuous venous oximetry, respectively, in 41 severely brain-injured patients. The purpose of the study was to examine the relationships between TCD flow velocity, SJO2, and alterations in blood pressure (BP), intracranial pressure (ICP), and cerebral perfusion pressure (CPP). In these patients, CPP was reduced either by rising ICP or by falling BP. Both forms of reduction of CPP resulted in a greater fall in diastolic flow velocity than other flow parameters. As CPP decreased below a critical value of 70 mm Hg, a progressive increase in TCD pulsatility index (PI) was observed (r = -0.942, p less than 0.0001), accompanied by a fall in SJO2 (r = 0.78, p less than 0.0001). At pressures above 70 mm Hg, there was no correlation of either PI or SJO2 with CPP. The relationship between PI and CPP held true in patients with both focal and diffuse pathologies and was the same whether changes in CPP resulted from alterations in ICP or BP. The PI and SJO2 correlated better with CPP than with ICP or BP. Transcranial Doppler ultrasonography can identify states of reduced CPP. Decreases in SJO2 with falling CPP suggested progressive failure of cerebral blood flow to meet metabolic demands. Monitoring of TCD and SJO2 may be used to define the optimum CPP level for management of severely brain-injured patients.