Fas and Fas ligand (FasL) have been assigned a pivotal role for establishment and maintenance of peripheral tolerance of immune system, and mice having defects in Fas/FasL genes develop diseases resembling human systemic lupus erythematosus (SLE). It has been reported that Fas expression of circulating lymphocytes is enhanced in patients with SLE. Nonetheless, apoptosis of SLE lymphocytes is not accelerated. Expression of FasL was detected marginally in unstimulated lymphocytes in normal individuals. In contrast, freshly isolated SLE lymphocytes showed enhanced expression of FasL without in vitro stimulation. We also found the presence of circulating anti-FasL autoantibody in patients with SLE. These results suggest that aberrant FasL expression of lymphocytes and anti-FasL autoantibody are, at least in part, involved in the immune-abnormalities and pathogenesis of the disease.