Organ-specific autoimmune diseases are usually considered to be mediated by autoreactive T cells which infiltrate the target tissue. Conceivably, these T cells could represent pathogenic autoreactive cells which recognize their specific antigen (peptide or superantigen) within the pathological tissue. Extensive studies dealing with the clonality of the infiltrating autoreactive cells gave conflicting results both in humans and animals. One possibility for explaining these contradictory data could rely on the stage of the disease when the T cell population is studied. Here, we report on this parameter by analyzing T cell receptor beta-chain variable regions of infiltrating T cells involved during one of the most frequent human organ-specific autoimmune disease, the primary Sjögren's syndrome. Six patients were selected on the basis of the duration of the disease before the biopsy procedure (two early and four late stages) to analyze initial and late T cell waves within the abnormal tissue. Using short-term interleukin-2-stimulated T cells, polymerase chain reactions, Southern and sequence analysis, we conclude that: (a) there is a clear restriction in the V beta usage by the infiltrating T cells only during the early stage of the disease, (b) this V beta restriction is related to a monoclonal T cell expansion, (c) the expanded V beta families are different from one patient to the other, and (d) there is no clear homology in length or amino acid composition in the CDR3 of the analyzed V beta regions. These results could provide an explanation to conflicting results on the V beta restriction usage during autoimmune diseases and could indicate time limitations in anti-V beta treatment. Furthermore, the monoclonal expansion of particular V beta-bearing T cells argues against a role for a superantigen during this disease.