In an attempt to elucidate the mechanism of development of organ-specific autoimmune lesions resembling human Sjögren's syndrome of MRL/lpr mice, we have analyzed local cytokine gene expressions and organ-specific autoantibody production in vivo. We have demonstrated that a major proportion of T cells bearing CD4 and V(beta)8 molecules are essentially responsible for triggering the autoimmunity in the salivary glands of MRL/lpr mice. The local cytokine gene expressions including interferon(IFN)-gamma, IL-12(p40) mRNAs were observed during the course of murine Sjogren's syndrome in MRL/lpr autoimmune strain. In particular, a high level of local expressions of IL-12 mRNA was detected earlier in the proinflammatory stage of autoimmune lesions. A significant level of local expression of MHC class-II(I-Ak) mRNA was detected before the onset of inflammatory lesions in the salivary glands, and I-Ak-positive epithelial duct cells were frequently observed in the salivary glands of MRL/lpr mice. In addition, we found the salivary gland-specific autoantibody in sera from MRL/lpr mice with early phase of autoimmune lesions by immunoblot analysis. These results suggest that cytokine gene stimulation and autoantibody production are essentially involved in the development of organ-specific autoimmune lesions in Sjögren's syndrome of MRL/lpr mice.