The effects of elevated intracranial pressure (ICP) on intracellular oxygenation and cerebrocortical blood volume (CBV) were studied in rabbits. Intracellular oxygen (O2) concentration was assessed as the level of pyridine nucleotide concentration ([NADH]) oxidation/reduction balance and relative cerebrocortical blood volume (CBV) were measured with a fibreoptic fluororeflectometer probe placed on the cerebrocortical surface. Experiments were conducted in six urethane anaesthetized, normocarbic animals at different fractions of inspired O2 (FIO2). During gradual increases in ICP, [NADH] began to increase (representing decreased intracellular mitochondrial PO2) for all values of FIO2 as ICP exceeded a threshold of 18 +/- 2.2 cmH2O (P less than 0.05). The decline in intracellular oxygenation with elevated ICP was inversely related to FIO2 (P less than 0.05). With ICP greater than 18 +/- 2.2 cmH2O, intracellular mitochondrial oxygenation showed an improvement between an FIO2 of 0.21 and 0.5 (P less than 0.05) but increasing FIO2 from 0.5 to 1.0 resulted in no statistically significant improvement in tissue redox balance. The CBV, largely representing tissue capillary blood, increased when ICP reached greater 18 +/- 1.2 cmH2O probably reflecting local autoregulation or venous distension (P less than 0.05). However, above 30 +/- 1.1 cmH2O, CBV decreased (P less than 0.05). The results demonstrate the interdependence of inspired oxygen concentration, elevated ICP, and brain intracellular oxygenation, and suggest that brain oxygen utilization deteriorates above an ICP of about 18 cmH2O.