Abnormal immune reactivity, with a production of multiple autoantibodies specially against the components of a nucleoplasm is one of the hallmarks of systemic lupus erythematosus (SLE). Our investigations were conducted on 102 patients with SLE, classified according to the criteria of ARA, aiming to better characterize the overall incidence of anti-nuclear antibodies in SLE, to determine the type of immunofluorescent staining of the nuclei, and to characterize the fine specificity of such antibodies using modified ELISA procedure. Results of our investigation show that 95% of patients with SLE have detectable anti-nuclear antibodies. Predominant pattern of nuclear staining is homogeneous, followed by a speckled type, while the rim (peripheral) pattern is relatively infrequent. Anti-nuclear antibodies showed the highest reactivity against native DNA (70% of patients), which was followed by binding to SS-A, eRNP and SS-B antigens. Interestingly, using ELISA procedure we could observe the reactivity against Sm antigen only in 5% of SLE patients. In patients who showed homogeneous or rim pattern of nuclear staining the predominant type of reactivity was against native DNA, while in patients with speckled type most frequent binding to non-histone proteins was observed. The most frequently observed individual pattern of ANA reactivity was of polyreactive type.