Expression of cytokine genes in freshly isolated T cell subsets in the autoimmune lpr mouse has been studied to determine what factors may be produced by these cells in vivo. RNA prepared from T cell subsets from diseased lpr mice and from the normal congenic strain, MRL/n, was tested for the presence of cytokine-specific message using the polymerase chain reaction. Cells of the expanded abnormal T cell subset were shown to express genes encoding interferon (IFN)-gamma, tumor necrosis factor (TNF)-beta, TNF-alpha and interleukin (IL)6, cytokines which are associated with inflammatory immune responses. These cells may thus play an important role in exacerbation of the pathological symptoms of the systemic autoimmune disease. These cells expressed no detectable IL1, IL2, IL3, IL4 or IL5. Phenotypically normal CD4+ and CD8+ T cells from both lpr and MRL/n also contained transcripts for IFN-gamma, TNF-alpha, TNF-beta and IL6. IL2 mRNA was found almost exclusively in the CD4+ subset, indicating that the CD8+ T cells in the lpr mouse are not highly activated through their class I major histocompatibility complex molecules to produce IL2, as could occur if a virus infection was inducing autoimmunity in these mice. Similar levels of IL2 mRNA were present in the CD4+ T cells of lpr and MRL/n mice, demonstrating that these cells are not defective in IL2 production in vivo.