We have compiled an online database of known human defense genes: the Immunogenetic Related Information Source (IRIS). As of October 1, 2004, there are 1562 immune genes recorded in IRIS, representing 7% of the human genome. This resource contains searchable information including chromosomal location, sequence data, and a curated functional annotation for each entry. We used IRIS as a basis for analyzing the composition and characteristics of the immune genome, such as gene clustering, polymorphism, and relationship to disease. High protein sequence similarity correlated inversely with distance between immune genes, consistent with clustering of duplicated loci. We also found that, even though some immune genes exhibit high levels of polymorphism, such as MHC class I, the range of levels of polymorphism in immune genes is similar to that of nonimmune genes. Approximately 20% of immune genes have a known disease association. IRIS is available online at .