To investigate the possible involvement of interferon-inducible T cell alpha chemoattractant (I-TAC or CXCL11) in the salivary gland lesions of Sjögren's syndrome (SS), I-TAC mRNA expression was assayed in cultured salivary epithelial cells by reverse transcriptase-polymerase chain reaction (RT-PCR). This transcript was not expressed by SS salivary epithelial cells in the absence of IFNgamma, but was expressed after cells were stimulated with IFNgamma. We found that IFNgamma was the only cytokine that induced I-TAC mRNA expression. I-TAC proteins were shown by ELISA to be secreted into the culture supernatants of SS salivary epithelial cells following IFNgamma stimulation. Moreover, immunohistochemical assays of minor salivary glands (MSG) showed that I-TAC was predominantly located in the ductal epithelium adjacent to lymphoid infiltrates in the SS salivary gland, indicating that ductal epithelial cells produce I-TAC proteins in response to stimulation with IFNgamma secreted by lymphocytes that infiltrate into SS salivary glands. In contrast, I-TAC proteins were virtually absent from normal salivary glands. These findings suggest that I-TAC is involved in the development of salivary gland lesions observed in SS.