Chronic beryllium disease (CBD) is a hypersensitivity disorder caused by beryllium exposure in the workplace and is characterized by the accumulation of beryllium-specific CD4(+) T cells in the lung and granulomatous inflammation. This disorder occurs in 2-16% of exposed workers, depending on genetic susceptibility and the nature of the exposure. Susceptibility has been associated with HLA-DP alleles possessing a glutamic acid at the 69th position (Glu(69)) of the beta-chain. The mechanism for this association lies in the ability of these HLA-DP molecules to present beryllium to pathogenic CD4(+) T cells. These findings in CBD have important implications for studies in autoimmune diseases, including those in which the inciting antigen is unknown and the target organ is inaccessible.