There is a substantial interest in the role of antineutrophil antibodies since Fc gamma receptors (Fc gamma Rs) have been identified as the target for the majority of such autoantibodies. Antineutrophil antibodies have long been detected by an indirect immunofluorescence technique. Following optimization of the flow cytometric method of detection, we developed three enzyme-linked immunosorbent assays (ELISAs), each specific for autoantibodies against one of the three classes of human Fc gamma R. Fc gamma RI and Fc gamma RII were purified from cultured cells, and Fc gamma RIII was produced as a recombinant molecule. These were then used as capture agents in the respective ELISAs. When applied in parallel to a sizeable group of patients with primary Sjögren's syndrome, both methods established that anti-Fc gamma R autoantibodies were heterogeneous. This finding indicates that different populations of partly cross-reactive antibodies are detectable by these two methods.