Introduction During the past half century, aniline dyes and fluorescent compounds have been used to study alterations in the blood-brain barrier occurring in a variety of neuropathological conditions. Theories that were evolved to explain the absence of staining of the normal brain by acid dyes included: the impermeability of cerebrovascular endothelium to negatively charged particles,1 a lack of brain tissue affinity for dyes,2 and a barrier imposed by ground substance.3 Although the binding of certain acid and basic dyes to protein had been studied in some detail by chemists,4 there was no attempt in the early neurological literature to relate exclusion of dye from brain to protein impermeability. The importance of binding to plasma protein as a mechanism limiting dye penetration into brain was first emphasized by Tschirgi.5 More recently, Clasen et al6 have demonstrated a quantitative relationship between the brain uptake of Evans