Studies on cerebral blood flow during hypotension and high intracranial pressure are scarce. Accordingly, this study examines the effects of increased cerebrospinal fluid (CSF) pressure on the cerebral circulatory response to hemorrhage. Measurements of cerebral microcirculation with laser Doppler flowmetry was performed in 12 pento-barbital-anesthetized pigs during hemorrhage, with and without high CSF pressure. Arterial and CSF pressures were monitored. Laser Doppler microprobes were positioned on the brain surface and in the gray and white matter. High CSF pressure (80% of mean arterial pressure) was induced by infusion of artificial CSF into the cisterna magna in eight pigs, whereas four animals served as controls. The response to rapid arterial bleeding at normal and high CSF pressure was recorded. When CSF pressure was normal, bleeding of 15% and 25% of the total blood volume caused a drop of cerebral perfusion pressure to 73 and 71 mmHg, respectively, causing a decrease in the laser Doppler signal to 90 ± 8% of the baseline value. During high CSF pressure, the cerebral perfusion pressure was 23 mmHg and the laser Doppler signal was 52 ± 29% of baseline. Bleeding of 15% of blood volume reduced the laser Doppler signal to 0 (equal to postmortem values) in three pigs, and bleeding of 25% of the blood volume reduced the laser Doppler signal to 0 in seven of eight pigs. Consequently, a blood loss that is of minor importance for the cerebral microcirculation in the normal state may be deleterious to the circulation when combined with high CSF pressure.