The gene encoding the human angiotensin II (AT2) receptor exists as a single copy and contains no intron in its coding region. Its nucleotide sequence is identical to that of cDNA clones isolated from human myometrial library. In addition, binding properties of the corresponding receptor expressed in COS cells are identical to those of endogenous AT2 receptors from human myometrium. The human AT2 receptor gene translates into a polypeptide of 363 amino-acid residues that belongs to the seven transmembrane domains receptor superfamily. This polypeptide shows 92% amino-acid sequence homology and the same pharmacological profile as AT2 receptors recently isolated from rat and mouse. The AT2 receptor gene maps to the X chromosome in man (region Xq24-q25) as well as in mouse (region XA2-A4). These findings open new perspectives regarding a potential involvement of AT2 receptors in X-linked congenital diseases. Expression of AT2 receptor mRNA is found in human myometrium, fallopian tubes and adrenals, and at extremely high levels in fetal kidney and intestine. These results indicate that AT2 receptor gene expression is regulated during human embryonic development, and support the hypothesis that AT2 receptors may play a role in organogenesis.