The present work is the first to report evidence for complement dependent cytotoxic auto-antibodies to neutrophils in patients with Rheumatoid Arthritis and neutropenia (Felty's Syndrome), and the neutropenia associated with SLE. Using a dye-exclusion microcytotoxicity assay activity was found in eight Felty's syndrome patients, but not in ten patients with rheumatoid arthritis without neutropenia; no significant activity was found in normal controls and subjects with multiple pregnancies or transfusions. Activity could be eluted from column adherent, serum exposed neutrophils by affinity chromatography; eluted protein contained IgG. Indirect immunofluorescent studies showed binding of IgG to neutrophils on exposure to Felty's serum but not normal serum. Antibodies reacted best at 37 degrees unlike antilymphocyte antibodies which are maximally reactive at 4 degrees C. This finding raises the possibility that these antibodies may have a pathogenetic role.