Previous studies have demonstrated that the IgM monoclonal anti-IgG autoantibodies (AGAs) characteristic of essential mixed cryoglobulinaemia (EMC) display preferential use of kappa light chains of the VKiiib sub-subgroup. In order to gain insights as to the possible basis for this V region selection, IgM-VKiiib immunoglobulin was affinity purified from normal human serum, analysed by dissociating two-dimensional gel electrophoresis and compared to the two-dimensional gel patterns of IgM-VKiiib anti-IgG autoantibodies (AGAs) from patients with essential mixed cryoglobulinaemia (EMC). The results suggest that only part of the available VKiiib light chain repertoire is selected by EMC AGAs. When AGAs from EMC, rheumatoid arthritis (RA) and primary Sjögren's syndrome (SS) patients were analysed by ELISA, it was found that the association of the VKiiib light chains with anti-IgG autoantibodies differed significantly among the three diseases. In fact, in RA there appeared to be a negative selection against the use of VKiiib in AGAs. Clearly, the VKiiib determinant is not required for anti-IgG autoreactivity. The possibility emerges, therefore, that the genesis and perpetuation of AGA synthesis in these diseases may follow quite different pathways.