1. The fluid homeostasis of the brain depends both on the endothelial blood-brain barrier and on the epithelial blood-cerebrospinal fluid (CSF) barrier located at the choroid plexuses and the outer arachnoid membrane. 2. The brain has two fluid environments: the brain interstitial fluid, which surrounds the neurons and glia, and the CSF, which fills the ventricles and external surfaces of the central nervous system. 3. CSF acts as a fluid cushion for the brain and as a drainage route for the waste products of cerebral metabolism. 4. Recent findings suggest that CSF may also act as a "third circulation" conveying substances secreted into the CSF rapidly to many brain regions.