Recently, the nonclassical human leukocyte antigen (HLA) gene, HLA-G, was identified as an asthma and bronchial hyperresponsiveness susceptibility locus on 6p21 by linkage studies followed by positional cloning in white families ascertained in Chicago as part of the Collaborative Study on the Genetics of Asthma. HLA-G is most highly expressed in placental cells at the maternal-fetal interface, where it inactivates maternal immune cells, skews the immune system toward a Th2 phenotype, and plays a key role in inducing maternal tolerance toward the genetically foreign fetus. It is also expressed in adult cells, such as bronchial epithelial cells, particularly during inflammatory responses. This gene also may participate in immune responses in the asthmatic lung and influence the cytokine profile in response to inhaled allergens.