Delivery of oligonucleotides (ODNs) to the brain is hindered by the tight junctions of the capillary endothelial cells that constitute the blood–brain barrier. We have examined the ability of a monoclonal antibody (OX-26), which recognises the rat transferrin receptor, to function as an effective carrier for the delivery of ODNs to the brain. In this initial report, we have characterised the uptake of OX-26–ODN conjugates in an immortalised, rat brain endothelial cell line, called RBE4, which is reported to be a good in vitro model of the blood–brain barrier. Uptake of the conjugate into this cell model was twofold higher than the free ODN and its uptake mechanism was consistent with transferrin receptor-mediated endocytosis. Exocytosis profiles of the OX-26–ODN conjugates were different from either free ODN or a non-specific IgG–ODN conjugate indicating an altered sub-cellular distribution, possibly involving `deeper' cellular compartments. Treatment of cells with monensin further increased the intracellular accumulation of the OX-26–ODN conjugates suggesting that trafficking of the conjugate may involve the trans-Golgi network. These data suggest that OX-26 conjugates improve delivery of ODNs into an immortalised cell culture model of the BBB and are worthy of further study as carrier systems for the CNS delivery of nucleic acids.