Our aims were to determine the prevalence of neutrophil antibodies in patients with primary Sjogren's syndrome (pSS), identify their target antigen(s), and evaluate their functional significance. Neutrophil antibodies were detected using an indirect immunofluorescence (IIF) test and an enzyme-linked immunosorbent assay (ELISA), using recombinant human Fc-gamma receptor (FcγRlllb) as a capture agent. Luminol-dependent chemiluminescence was then measured by an established technique. Antibodies to neutrophils were detected in 30 of 66 patients (45%) and categorized on the basis of posrtivity for the two assays: IIF+/ ELISA+ (group A: five patients), IIF+/ELISA- (group B: five patients), and IFF-/ELISA+ (group C: 20 patients). All positive sera contained antibodies directed to the neutrophil-specific FcγRlllb, and none of them bound to NAnullneutrophils. The titer of neutrophil-reactive antibodies (groups A and B) showed no correlation with the neutrophil count, but these autoantibodies did reduce the cell ability to generate a respiratory burst. Thus, neutrophil antibodies are common in patients with pSS. Their main target appears to be FcγRIII, and this may partly account for the dysfunction in FcγR-mediated clearance by the reticuloendothelial system reported in these patients.