Interleukin-10 (IL-10) production by B lymphocytes has previously been demonstrated for malignant cells and for in vitro activated normal B cells. Spontaneous in vivo production of IL-10 by normal B lymphocytes has only been demonstrated in mice, in which autoreactive Ly 1 + B cells are involved. In the present study, spontaneous expression of the IL-10 gene by peripheral blood mononuclear cells was investigated in systemic lupus erythematosus (SLE), a human disease involving autoreactive B cells. Of the 47 SLE patients tested by coupled reverse transcriptase-polymerase chain reaction, 34 scored positive, contrasting with only 1 positive out of 34 normal subjects (p < 0.001). Spontaneous in vitro production of IL-10 by PBMC, determined using an ELISA assay, was 33 times higher in SLE than in controls (2623 +/- 728 pg/ml vs 79.3 +/- 34.5 pg/ml, respectively) (p < 0.001). The level of production of IL-10 in SLE was unrelated to either clinical or biological markers of disease activity. Among PBMC, monocytes and B lymphocytes both contributed to IL-10 production, whereas T cells did not. IL-10 overproduction in SLE suggests that this Th2-type interleukin plays a role in the production of autoantibodies through pathways involving both paracrine production by monocytes and autocrine IL-10 production by autoreactive B cells.