The recruitment of cytotoxic T lymphocytes (CTL) is considered to be the major tool for the clearance of HIV from the lower respiratory tract. In this study we evaluated the pathophysiologic role of two lymphotactic CXC chemokines (IP-10 and Mig) in the lung of HIV-infected patients. These chemokines stimulate the directional migration of activated T cells and interact with a specific receptor (CXC receptor 3, CXCR3). Lymphocytes recovered from the bronchoalveolar lavage (BAL) of HIV-infected patients with high intensity T-cell alveolitis were CD8+ T cells expressing high levels of CXCR3 and IFN-gamma, a phenotype that is characteristic of Tc1 cells. Pulmonary T cells expressing CXCR3 exhibited a high migratory capability in response to IP-10 and Mig. Alveolar macrophages recovered from patients with T-cell alveolitis bore the IFN-gamma-inducible proteins IP-10 and Mig. A positive correlation was demonstrated between IP-10, Mig, and IL-15 expression by alveolar macrophages. Interestingly, macrophages isolated from the lung of HIV-infected patients with T-cell alveolitis secreted definite levels of CXCR3 ligands capable of inducing T-cell chemotaxis. Taken together, our data suggest that chemotactic ligands that bind CXCR3 contribute significantly to the accumulation of HIV-specific CTL in the lung.