This study identifies a human serotonin transporter (hSERT) that is sensitive to antidepressants and cocaine. The hSERT is expressed in human neuronal, platelet, placental, and pulmonary membranes. The brain 5HT transporter is a primary site of action for antidepressants and may mediate behavioral and toxic effects of cocaine and amphetamines. The hSERT was cloned and characterized, showing high affinity for serotonin, and is sensitive to selective 5HT transport inhibitors, including paroxetine, fluoxetine, and imipramine. It is also antagonized by cocaine and amphetamine. Sequence analysis reveals that hSERT is 92% identical to the cloned rat brain 5HT transporter, with identical predicted topological features and conserved sites for posttranslational modifications. Unlike the rodent, where a single mRNA appears to encode 5HT transporters, multiple hybridizing RNAs are observed in human placenta and lung. Somatic cell hybrid and in situ hybridization studies are consistent with a single gene encoding the human 5HT transporter, localized to chromosome 17q11.1–17q12. The study also shows that the hSERT is a functional human 5HT transporter, with a 630-amino acid open reading frame. The hSERT is sensitive to monoamine and 5HT-selective transport antagonists. The gene encoding the human 5HT transporter was mapped to chromosome 17q11.1–17q12. The study also shows that the hSERT is a member of a large gene family encoding other Na⁺- and Cl⁻-dependent transport proteins, including neurotransmitters such as GABA, norepinephrine, and dopamine. The rodent 5HT transporter is most closely related to human norepinephrine and rodent dopamine transporters, forming a small subdivision of biogenic amine transporters within the larger transporter family. The study also shows that the hSERT is a functional human 5HT transporter, with a 630-amino acid open reading frame. The hSERT is sensitive to monoamine and 5HT-selective transport antagonists. The gene encoding the human 5HT transporter was mapped to chromosome 17q11.1–17q12.This study identifies a human serotonin transporter (hSERT) that is sensitive to antidepressants and cocaine. The hSERT is expressed in human neuronal, platelet, placental, and pulmonary membranes. The brain 5HT transporter is a primary site of action for antidepressants and may mediate behavioral and toxic effects of cocaine and amphetamines. The hSERT was cloned and characterized, showing high affinity for serotonin, and is sensitive to selective 5HT transport inhibitors, including paroxetine, fluoxetine, and imipramine. It is also antagonized by cocaine and amphetamine. Sequence analysis reveals that hSERT is 92% identical to the cloned rat brain 5HT transporter, with identical predicted topological features and conserved sites for posttranslational modifications. Unlike the rodent, where a single mRNA appears to encode 5HT transporters, multiple hybridizing RNAs are observed in human placenta and lung. Somatic cell hybrid and in situ hybridization studies are consistent with a single gene encoding the human 5HT transporter, localized to chromosome 17q11.1–17q12. The study also shows that the hSERT is a functional human 5HT transporter, with a 630-amino acid open reading frame. The hSERT is sensitive to monoamine and 5HT-selective transport antagonists. The gene encoding the human 5HT transporter was mapped to chromosome 17q11.1–17q12. The study also shows that the hSERT is a member of a large gene family encoding other Na⁺- and Cl⁻-dependent transport proteins, including neurotransmitters such as GABA, norepinephrine, and dopamine. The rodent 5HT transporter is most closely related to human norepinephrine and rodent dopamine transporters, forming a small subdivision of biogenic amine transporters within the larger transporter family. The study also shows that the hSERT is a functional human 5HT transporter, with a 630-amino acid open reading frame. The hSERT is sensitive to monoamine and 5HT-selective transport antagonists. The gene encoding the human 5HT transporter was mapped to chromosome 17q11.1–17q12.