We recently reported that transcription of human endogenous retrovirus (HERV) clone 4-1-like sequences is increased in patients with systemic lupus erythematosus (SLE). We therefore investigated the role of DNA methylation in the transcription of this HERV. The effect of a demethylating agent, 5-aza-deoxycytidine (5-aza C), on the transcription of HERV clone 4-1 in healthy individuals and patients with SLE was examined using reverse transcriptase-PCR and real-time quantitative PCR. 5-aza C increased clone 4-1-like messenger RNA in healthy controls, but not in patients with SLE. Defects of methylation may contribute to the transcription of HERV in patients with SLE and this may be related to the pathogenesis of SLE.