Studies reporting the composition of cerebrospinal fluid obtained from hydrocephalic humans have been critically reviewed. Hydrocephalus-induced alterations in the cerebrospinal fluid concentrations of neurotransmitters and peptide neuromodulators, products of glycolysis and nucleotide metabolism, neural cell-derived proteins and enzymes, and serum-derived proteins have been documented. The data are interpreted with reference to experimental studies. The reported changes suggest that in the hydrocephalic brain there are disturbances of oxidative metabolism and neurotransmission, and perhaps damage to periventricular cells particularly when intracranial pressure is elevated. Although no assays have provided and entirely useful guide to aid decisions regarding shunt therapy, they have provided in vivo information regarding the pathophysiology of hydrocephalus.