Because the choroid plexus normally controls the production and composition of cerebrospinal fluid and as such, its many functions of the central nervous system, we investigated whether ligand-mediated targeting could deliver genes to its secretory epithelium. We show here that when bacteriophage are targeted with epidermal growth factor, they acquire the ability to enter choroid epithelial cells grown in vitro as cell cultures, ex vivo as tissue explants or in vivo by intra-cerebroventricular injection. The binding and internalization of these particles activates EGF receptors on targeted cells and the dose-, and time-dependant internalization of particles is inhibited by the presence of excess ligand. When the phage genome is further re-engineered to contain like green fluorescent protein or firefly luciferase under control of the cytomegalovirus promoter, gene expression is detectable in the choroid plexus and ependymal epithelium by immunohistochemistry or by non-invasive imaging respectively. Taken together, these data support the hypothesis that re-engineered ligand-mediated gene delivery should be considered a viable strategy to increase the specificity of gene delivery to the central nervous system and bypass the blood brain barrier so as to exploit the biological effectiveness of the choroid plexus as a portal of entry into the brain.