IgG4-related disease (IgG4-RD) is a novel and rare autoimmune disease entity. Elevated serum IgG4 level is strongly suggestive of IgG4-RD. But it is still unknown whether serum IgG4 elevation commonly occurs in other autoimmune diseases. In this study, the serum IgG4 levels were detected by an established enzyme-linked immunosorbent assay (ELISA) in a variety of autoimmune diseases including systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), polymyositis or dermatomyositis (PM/DM) and IgG4-RD. To evaluate the reliability of this ELISA system, some of our samples were sent to a lab in Kanazawa Medical University, Japan, and detected by using the nephelometric assay. The results showed that our findings were consistent with theirs. Moreover, it was found that the serum IgG4 levels were 0.23 +/- 0.16 g/L in 53 healthy controls, 0.16 +/- 0.15 g/L in 103 SLE patients, 0.22 +/- 0.18 g/L in 41 SS patients and 0.40 +/- 0.32 g/L in 21 PM/DM patients. No significant difference in the serum IgG4 level was observed among these groups (P>0.05). The serum IgG4 levels of two cases of IgG4-RD were 1.63 and 4.65 g/L respectively, and both decreased markedly after treatment with glucocorticoids. These data indicated that this established ELISA system can be used for detecting serum IgG4 levels. Elevated serum IgG4 levels help diagnose IgG4-RD and evaluate the curative effect of this condition rather than other autoimmune diseases.