Afamin, an 87 kDa human plasma glycoprotein with specific binding properties for vitamin E (alpha-tocopherol) was recently characterized (Jerkovic, 1997; Vögele, 1999). In the present study the in vitro effects on neuronal cells of native human Afamin, of Afamin pre-loaded with vitamin E (Afamin+), and of vitamin E were investigated. Isolated cortical chicken neurons were maintained either under apoptosis-inducing low serum conditions or exposed to oxidative stress by the addition of H2O2 or beta-amyloid peptide(25-35). Afamin and vitamin E synergistically enhance the survival of cortical neurons under apoptotic conditions. Furthermore, Afamin alone protects cortical neurons from cell death in both experimental settings. Therefore, the plasma glycoprotein Afamin apparently displays a neuroprotective activity not only by virtue of binding and transporting vitamin E but also on its own.