Accelerated apoptosis and improper expression of cytokine genes have been considered as important defects of lymphocytes for the development of systemic lupus erythematosus (SLE). This study was undertaken to test the possible contribution of serum factors obtained from SLE patients to these abnormalities. Molt-4 and Jurkat cells constantly exhibited a slower growth rate as well as more dead cells in culture with SLE sera tested than controls, although the cell cycle progression was apparently unaffected. Increased apoptosis was demonstrable among SLE sera-cultured cells by ELISA for apoptosis-specific DNA fragments and terminal deoxynucleotidyl transferase (TdT) in situ death analysis. Different levels of Fas, Fas-L, and Bcl-2 gene products were not detected between SLE sera-treated cells and the controls. The transcripts of interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) genes of these two T cell lines were evidently increased in the presence of SLE sera, while IL-2 and IL-4 were unaffected. Elevated expression of IL-5 was also found in Molt-4 cells. By contrast, SLE sera reduced the transcripts of IL-6 gene in Jurkat cells. The effects of SLE sera were independent of corticosteroid medication. These results suggest that serum abnormalities may also play a role in T cell dysfunction.