The hypothesis that cerebral arteriovenous difference of oxygen content (AVDO2) can be used to predict cerebral blood flow (CBF) was tested in patients who were comatose due to head injury, subarachnoid hemorrhage, or cerebrovascular disease. In 51 patients CBF was measured daily for 3 to 5 days, and in 49 patients CBF was measured every 8 hours for 5 to 10 days after injury. In the latter group of patients, when a low CBF (less than or equal to 0.2 ml/gm/min) or an increased level of cerebral lactate production (CMRL) (less than or equal to -0.06 mumol/gm/min) was encountered, therapy was instituted to increase CBF, and measurements of CBF, AVDO2, and arteriovenous difference of lactate content (AVDL) were repeated. When data from all patients were analyzed, including those with cerebral ischemia and those without, AVDO2 had only a modest correlation with CBF (r = -0.24 in 578 measurements, p less than 0.01). When patients with ischemia, indicated by an increased CMRL, were excluded from the analysis, CBF and AVDO2 had a much improved correlation (r = -0.74 in 313 measurements, p less than 0.01). Most patients with a very low CBF would have been misclassified as having a normal or increased CBF based on the AVDO2 alone. However, when measurements of AVDO2 were supplemented with AVDL, four distinct CBF patterns could be distinguished. Patients with an ischemia/infarction pattern typically had a lactate-oxygen index (LOI = -AVDL/AVDO2) of 0.08 or greater and a variable AVDO2. The three nonischemic CBF patterns had an LOI of less than 0.08, and could be classified according to the AVDO2. Patients with a normal CBF (mean 0.42 +/- 0.12 ml/gm/min) had an AVDO2 between 1.3 and 3.0 mumol/ml. A CBF pattern of hyperemia (mean 0.53 +/- 0.18 ml/gm/min) was characterized by an AVDO2 of less than 1.3 mumol/ml. A compensated hypoperfusion CBF pattern (mean 0.23 +/- 0.07 ml/gm/min) was identified by an AVDO2 of more than 3.0 mumol/min. These studies suggest that reliable estimates of CBF may be made from AVDO2 and AVDL measurements, which can be easily obtained in the intensive care unit.