This study was performed to examine effects of increased intracranial pressure on cerebral blood flow (CBF) and to determine if sympathetic nerves modulate this response. Intracranial pressure was raised by infusion of artificial cerebrospinal fluid into a lateral ventricle of rabbits. Increases in intracranial pressure were similar in the lateral ventricles and cisterna magna. Graded increases in intracranial pressure from base line of 7 to 96 mmHg produced graded reductions in CBF (measured with microspheres). Reductions in blood flow were heterogeneous: elevation of intracranial pressure from 7 +/- 1 to 46 +/- 3 (SE) mmHg reduced blood flow to the cerebrum by 33 +/- 5% and blood flow to the medulla by only 5 +/- 2% (P less than 0.05). Reduction of intracranial pressure to normal levels produced marked reactive hyperemia in all areas of the brain. Although sympathetic nerve traffic increased fivefold during intracranial hypertension, superior cervical ganglionectomy did not affect CBF. In other experiments, electrical stimulation of sympathetic nerves at 4 Hz reduced blood flow to skeletal muscle by 80% but did not affect CBF; stimulation at 15 Hz produced a modest reduction in CBF. We conclude that 1) during increases in intracranial pressure, blood flow is better preserved to the medulla than to the cerebrum despite similar intracranial pressure in the two areas and 2) intense reflex activation of sympathetic nerves during intracranial hypertension does not affect CBF.