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Publisher Summary This chapter presents studies of the androgen insensitivity syndrome (AIS). AIS is also referred to as testicular feminization (Tfm) in rats, mice, and humans. Studies have established that this disorder is linked to the X chromosome. Androgen insensitivity is characterized by lack of a target cell response to androgen. To localize the androgen receptor (AR) gene, a series of Tfm mouse–human cell hybrids containing X chromosome are produced. Expression of AR androgen binding indicated that either the AR locus or a factor controlling AR expression is located on the human X chromosome near the centromere. Cloning the AR enables a demonstration that it is the AR structural gene that occupies this locus on the X chromosome and establishes that a mutation in the AR gene can result in AIS. AR belongs to the subfamily of steroid hormone receptors within a larger family of nuclear proteins that likely evolved from a common ancestral gene. Each contains an amino-terminal region, which is variable in length and could have a role in transcriptional activation, a central cysteine-rich DNA-binding domain, and a carboxyl-terminal ligand-binding domain. The chapter presents a comparison of human and rat AR cDNAs—complementary DNAs.