For inner ear drug delivery, we noted another hopeful but unevaluated route, the longitudinal route from the endolymphatic sac to the cochlea and vestibule, suggested by several lines of evidence in animal studies. Morgenstern et al. and Lee et al. demonstrated that the intra-endolymphatic sac materials could reach the cochlear endolymphatic site through the vestibular aqueduct using a test marker and an oto-toxic drug, respectively. Recently, Yamasoba et al. suggested the possibility of gene therapy through the vestibular aqueduct route. We also revealed that intra-endolymphatic sac steroids could up-regulate a water channel molecule, aquaporin-3 mRNA in the cochlea.