ENT1 protein, which encodes the es nucleoside transporter, is present on the human BBB. It is thought that this carrier is responsible for the transport of ddI across the guinea pig BBB. This was confirmed when the es transporter substrates, adenosine and thymidine, inhibited the brain uptake of [3H]ddI (Gibbs et al., 2003a). Interestingly, the es transporter is also active in human lymphocytes, raising the possibility that it could facilitate the transport of NRTIs into this HIV reservoir (Chan et al., 1993). ENT2, the ei transporter, transports purine and pyrimidine nucleosides but with a lower affinity that ENT1. However unlike ENT1, ENT2 is a carrier of AZT and can transport ddI and ddC much more efficiently than ENT1 (Baldwin et al., 2004).