We evaluated the systemic and cerebral effects induced by an increase to 100% of the inspired oxygen fraction (FiO2) on 20 comatose patients with head injury (9 patients) and SAH (11 patients). Brain tissue oxygen tension (PtiO2) was measured through a Clark electrode inserted in penumbra-like areas. We performed 55 hyperoxia tests by increasing FiO2 from 35 +/- 8% to 100% in one second and calculating the PtiO2 index as: PtiO2 variation from baseline at 1 minute/arterial oxygen tension (PaO2) variation from baseline at 1 minute x 100. One hundred percent FiO2 caused an increase of both arterial (from 139 +/- 28 to 396 +/- 77 mmHg) and cerebral (from 22.6 +/- 14 to 65.4 +/- 60 mmHg) oxygenation after 1 minute. The range of the PtiO2 response was not uniform and two groups were identified. The change was small, 0.8 mmHg/min/100 mmHg PaO2 (+/- 0.7; range 0-2) when mean PtiO2 was 19.7 +/- 13.1 mmHg, while a stronger response, 8 mmHg/min/100 mmHg PaO2 (+/- 5; range 3-18) (p < 0.01) was found when mean PtiO2 was 31.7 +/- 14.3 mmHg. Since O2 diffusion should follow the gas diffusion law, the increase in diffusion distance due to a reduction of capillary density in focal lesions may explain this relationship.