The sera of autoimmune and other mouse strains were analysed by high resolution two dimensional gel electrophoresis and silver staining. The most striking finding was the presence of unusually acidic immunoglobulin light chains in sera from 4-5 month old MRL/Mp-lpr/lpr mice. Similar light chains were found in lesser amounts in NZB/NZW and BXSB sera, and traces were observed in MRL/Mp-+/+, NZB, and in normal sera. The intensity of the acidic light chain spots increased with age in MRL/Mp-lpr/lpr mice, coincident with the development of autoimmunity. These acidic light chains circulated as components of complete IgG molecules, as they were no longer demonstrable in serum which had been rendered free of IgG by absorption with Cowans strain staphylococci. Because both cryoglobulins and glomerular eluates from MRL/Mp-lpr/lpr mice contained acidic immunoglobulin light chains, these molecules may be involved in immune complex formation and resultant injury.