Formulation of rational interventions in infantile hydrocephalus is limited by the inability to monitor cerebral hemodynamics quantitatively, continuously, and noninvasively. Near-infrared spectroscopy (NIRS) measures changes in cerebral concentration of oxygenated and deoxygenated hemoglobin (HbO 2 and Hb); HbD is the derived difference between HbO 2 and Hb. Our previous work showed that HbD reflected cerebral blood flow (CBF) measured by radioactive microspheres in a piglet model of systemic hypotension. This study was designed to determine whether NIRS detected important changes in cerebral perfusion and oxygenation in a piglet model of hydrocephalus and whether changes in HbD accurately reflected changes in CBF. Acute hydrocephalus was produced in neonatal piglets by intraventricular infusion of "mock cerebrospinal fluid." Intracranial pressure (ICP) was maintained for several minutes at approximately 10, 20, and 30 mm Hg above the baseline ICP. CBF was measured in cerebral cortex, white matter, and basal ganglia at each ICP by radioactive microspheres. Changes in HbO 2 and Hb were measured continuously by NIRS. Cerebral perfusion pressure declined with increasing ICP, and this decline was accompanied by significant decreases in HbD measured by NIRS and CBF measured by radioactive microspheres. There was a strong correlation between changes in HbD and individual changes in CBF in cerebral cortex, white matter, and basal ganglia (all p Ͻ 0.0001). This study demonstrates that changes in HbD reflect changes in CBF over a wide range of ICP in a model of acute hydrocephalus. This reproducible and easily obtained measurement by NIRS could facilitate considerably decisions concerning therapeutic interventions. Abbreviations NIRS, near-infrared spectroscopy HbO 2 , oxygenated Hb Hb, deoxygenated Hb HbD, Hb difference signal HbT, total Hb CytOx, oxidized cytochrome aa 3 ICP, intracranial pressure MAP, mean arterial pressure CPP, cerebral perfusion pressure CBF, cerebral blood flow rCBF, regional cerebral blood flow dpf, differential path-length factor Rational management of infantile hydrocephalus requires information about the disturbances in cerebral perfusion and metabolism that may contribute to the development of brain injury. Substantial evidence indicates that impairments of cerebral perfusion and metabolism play a role in the pathogenesis of brain injury secondary to hydrocephalus (1-8). However, currently there are major limitations in the ability to define changes in cerebral hemodynamics and metabolism quantitatively, continuously, and noninvasively at the bedside of the human infant.Doppler ultrasound provides information only about CBF velocity and cerebrovascular resistance but is not a consistently reliable measure of CBF (9). Positron emission tomography, magnetic resonance imaging, and magnetic resonance spectroscopy can supply detailed regional information regarding cerebral perfusion and metabolism but provide data at only a single point in time and require the transport of the critically ill infan...