To determine the relation between neutrophil function and the clinical characteristics of systemic lupus erythematosus (SLE), the superoxide anion (O2-) production by neutrophils, mediated by FcgammaR and FcgammaR/CR cooperation, was studied in 64 SLE patients classified according to their prevalent clinical manifestations. Three clinically distinct patterns were designated: (1) manifestations associated with the occurrence of cytotoxic antibodies (SLE-I group); (2) manifestations associated with circulating immune complexes (IC; SLE-II group), and (3) manifestations associated with IC and cytotoxic antibodies (SLE-III group). O2- production was evaluated by a lucigenin-dependent chemiluminescent assay in neutrophils stimulated with IC-IgG opsonized or not with complement. No difference in O2- production was observed when neutrophil responses from healthy controls were compared to the unclassified patients. However, when the SLE patient groups were considered, the following differences were observed: (1) SLE-I neutrophils showed lower O2- production mediated by the IgG receptor (FcgammaR) with the cooperation of complement receptors (FcgammaR/CR) than observed in the SLE-II, SLE-III, and healthy groups; (2) neutrophils from the SLE-II group showed a decreased [Formula: see text] production mediated by FcgammaR/CR compared to the SLE-III group, (3) SLE-III neutrophils produced more O(2)(-) than neutrophils from the SLE-II and control groups, and (4) CR showed inefficiency in mediating the O2- production by neutrophils from the SLE-I group. Comparative experiments on the kinetics of chemiluminescence (CL; Tmax and CLmax) disclosed differences only for the SLE-I group. Taken together, these results suggest that differences in oxidative metabolism of neutrophils mediated by FcgammaR/CR may reflect an acquired characteristic of disease associated with distinct clinical manifestations.