OBJECTIVE To examine the prevalence, subspecificities, and clinical associations of antineutrophil cytoplasmic antibodies (ANCA) in patients with systemic lupus erythematosus (SLE). METHODS One hundred fifty-seven sera from 120 patients with SLE were examined for classic (c) and perinuclear (p) pattern ANCA by indirect immunofluorescence. Antibody subspecificities were determined by enzyme-linked immunosorbent assay (ELISA). Serologic results were correlated with clinical manifestations as categorized by the BILAG (British Isles Lupus Assessment Group) index. RESULTS ANCA were found in 40 of the 157 sera (25%). Only a pANCA, not a cANCA, pattern of fluorescence was seen. By ELISA testing, 16 sera reacted to lactoferrin, 8 to elastase, and 4 to lysozyme. There was no reactivity to proteinase 3 (PR3) or myeloperoxidase (MPO). No correlation of pANCA, or any of the ANCA subspecificities, with organ system involvement, as categorized by the BILAG index, was found. Notably, there was no correlation of ANCA results with lupus vasculitis. CONCLUSIONS The absence of cANCA, anti-PR3, and anti-MPO shows that with appropriate assay conditions, ANCA testing assists in the differentiation between SLE and the ANCA-associated vasculitides. The lack of a correlation between pANCA or any ANCA subspecificity and clinical manifestations suggests that ANCA do not identify particular clinical subsets among SLE patients, including those with lupus vasculitis.