The dopamine transporter (DAT), a protein located on presynaptic nerve terminals (1–3), plays a major role in the reuptake of released dopamine. Uptake of DA is sodium- and chloride-ion- as well as temperature- and time-dependent, and is inhibited by a variety of compounds, including cocaine. Even though cocaine binds to several sites in the brain, cocaine abuse has been shown to be related to binding at the DAT site. Thus, analysis of the binding potencies of a series of cocaine analogs demonstrates that, in animal models, the reinforcing properties of these analogs correlate only with binding potencies at the DAT site. The DAT site has been called a cocaine receptor (4,5); it may be the initial site responsible for producing cocaine's drug reinforcement. The cDNA for the DAT has been cloned from rat (6–8), mouse (9,10), bovine (11), and human (12) brains, and these clones exhibit 92, 93, and 88% homology to human DAT (hDAT), respectively. A transporter with 92% homology and with neuronal DAT properties has also been characterized from African Green Monkey kidney (COS-7) cell lines (13). The hydrophobicity profile of the DAT indicates 12 possible membrane-spanning regions with the amino and carboxy termini located intracellularly. The protein from human and rat brains contains three and four extracellular N-glycosylation sites, respectively (Fig. 1). A detailed review of structural information about the DAT has recently been published (14).