The relationship of rheumatoid factors (RF) with antiphospholipid syndrome (aPLS) and anticardiolipin antibodies (aCL) has rarely been investigated in systemic lupus erythematosus (SLE). We found IgM-RF, IgG-RF, IgA-RF, IgM-aCL, IgG-aCL, IgA-aCL, respectively, in 35.4%, 35.4%, 33.8%, 23.1%, 23.1%, 20.0% of 65 SLE patients. Class specific RFs were negatively associated (P<0.05) with IgG-aCL. The frequency of definite or probable aPLS according to Alarcon-Segovia classification criteria was significantly (P<0.05) different (8.7% vs 30.9%) in patients with or without IgG-RF. Among the other clinical features of SLE, we found that patients with IgG-RF, compared to patients lacking this autoantibody, showed a lower frequency (P<0.05) of serositis (21.7% vs 52.4%) and hematologic (52. 2% vs 80.9%) disorders. The levels of IgG-RF and IgM-RF negatively correlated with the number of ARA criteria (P<0.05) but not with the indices of diseases activity or damage. Our study shows that in SLE the presence of RFs are not markers of severity of the disease, but the negative association between IgG-RF and IgG-aCL suggests a distinct role of these autoantibodies in the pathology of SLE, whereas the presence of IgG isotype may identify a subset of SLE patients having a lower risk to develop some clinical manifestations such as aPLS.