Fas (CD95) is a cell surface receptor whose biological function in circulating peripheral T cells is not well understood. To address the question of abnormal T cell sensitivity to Fas stimulation in systemic lupus erythematosus (SLE), we studied Fas‐transduced stimulation and apoptosis in peripheral blood T cells from patients with SLE and normal control. Immobilized anti‐Fas monoclonal antibodies (mAb) (imCH‐11; IgM type) significantly stimulated SLE T cell proliferation compared to T cells from normal donors and patients with rheumatoid arthritis ( p < 0.003 and p < 0.005, respectively). The soluble form of CH‐11 and other immobilized anti‐Fas mAb (UB‐2, ZB‐4; IgG type) failed to stimulate lupus T cells while immobilized human Fas ligand did. Furthermore, imCH‐11 induced IL‐2 and IL‐6 mRNA expression. However, imCH‐11 activation failed to induce expression of the T cell activation surface molecules CD25 and CD69. Addition of exogenous ceramide, a second messenger for Fas‐mediated apoptosis signaling, also induced T cell proliferation in SLE and normal controls. Moreover, fumonisin B1, a specific ceramide synthase inhibitor, and caspase inhibitors markedly suppressed imCH‐11 induced T cell proliferation, suggesting that the ceramide pathway may be involved in Fas‐transduced stimulation signals in SLE T cells. These results show that SLE T cells have an alteration in the Fas signal transduction pathway leading to cell proliferation. This defect may be important in Fas‐mediated peripheral immune homeostasis.