Objectives A bias of the use of T-cell receptor (TCR) Vβ regions has been reported both in peripheral blood and in several tissues in patients with AIDS, including lymph nodes, spleen and salivary glands. Although the disease is frequently characterized by an infiltration of T cells in the lung interstitium, no information is presently available on the configuration of the TCR repertoire in this microenvironment. This study was performed to address the question of whether a bias in T-cell selection occurs in the lung of patients with AIDS. Methods TCR β-chain variable region (TCR-Vβ) repertoire was analysed by flow cytometry and polymerase chain reaction (PCR) analyses in blood and lung lymphocytes of 13 patients with HIV-1 infection at different stages of the disease. Blood and lung lymphocytes were also assessed for their responsiveness to different superantigenic stimuli represented by staphylococcal enterotoxins (SEA, SEB, SEC1, SEC2, SED and SEE). Results Flow cytometry analysis in AIDS patients demonstrated an overexpression of cells bearing Vβ2 and Vβ3 gene segments in the lung compared with peripheral blood of the same subjects, as well as to lung and blood lymphocytes of normal controls. PCR analysis performed in AIDS patients extended these observations and demonstrated a significant bias also in the use of T cells bearing Vβ7 and Vβ9 gene regions in the lung compartment with respect to the blood. Virtually all T cells bearing the over-represented Vβ segment belong to the CD8 subset. Interestingly, T-lymphocyte response to different superantigens demonstrated a low proliferative rate in the lung with respect to the blood in HIV-1-infected patients. Conclusions These findings indicate a compartmentalization of cells bearing discrete Vβ gene products in the pulmonary microenvironment of patients with AIDS and suggest that the expansion of specific-Vβ region subsets occurring in the lung might result from triggering by a superantigen.