It has been demonstrated that abnormal expression of interleukin 6 (IL-6) may be involved in the pathogenesis of a variety of autoimmune diseases and glomerulonephritis. In this study, we demonstrate an age-associated increase in IL-6 in the sera of MRL/lpr mice but not in control congenic MRL/+ mice, normal strains of BALB/c, C3H/HeN mice, and other autoimmune prone mice, such as (NZB x NZW)F1, (NZB x BXSB)F1 mice. IL-6 activity was detected in the sera of MRL/lpr mice by 3 weeks of age and it was neutralized by anti-mouse IL-6 antibody. The serum IL-6 level was gradually increased with age and reached up to 410 pg/ml around 30 weeks of age. The expression of IL-6 mRNA was detected in the spleen and lymph nodes from 8 weeks of age. Expression of IL-6 mRNA was also detected in C57BL/6-lpr mice, indicating the possible linkage of abnormal expression of the IL-6 gene and the lpr gene. Southern blot analysis demonstrated that both the promoter region and 3' untranslated region of the IL-6 gene were apparently normal, suggesting that deregulated production of IL-6 may be due to abnormal transcriptional control. The data suggest that abnormal expression of the IL-6 gene may play a key role in the development of polyclonal B cell activation and glomerulonephritis in MRL/lpr mice.