The human 5-HT5A serotonin receptor has been cloned. As with the mouse and rat 5-HT5A receptors, the gene consists of two coding exons separated by a large intron. The deduced amino acid sequence of the gene reveals a protein of 357 residues which shares 93% (nucleotide) and 84% (amino acid) identity to the cloned mouse 5-HT5A receptor. We have determined the tissue distribution of the receptor by reverse transcriptase-PCR and found expression in all regions of the brain examined with little or no expression in peripheral tissues. The receptor has been transiently expressed in Cos M6 cells and exhibits a pharmacological profile closely resembling the mouse and rat 5-HT5A receptors with high, specific binding for ergotamine and methiothepin.