Sulfate is an essential anion involved in many biosynthetic and pharmacological reactions. Sulfate is an important constituent of myelin membranes in the brain; however, very little is known as to how sulfate enters brain cells. In this study, our aim was to determine whether the mammalian brain possesses a sulfate transporter. Injection of rat brain poly A(+) RNA into Xenopus oocytes led to an induction of Na(+)-independent sulfate transport, which was inhibited by oxalate, probenecid, phenol red, thiosulfate and DIDS. Hybrid depletion using sat-1 antisense oligodeoxyribonucleotides led to a complete inhibition of brain mRNA-induced sulfate transport in Xenopus oocytes, suggesting the presence of a functional sat-1 transcript in the brain. By RT-PCR, sat-1 mRNA was detected throughout the rat brain and in situ hybridisation showed highest sat-1 expression in the hippocampus and cerebellum. This is the first study to identify and characterise a functional mammalian brain sulfate transporter.