Although immunoglobulin G and free light (L) chains of oligoclonal origin in cerebrospinal fluid (CSF) are the most common immunologic abnormalities in multiple sclerosis (MS), it is unknown whether homologous CSF L chain sequences are present in different individuals with MS. Using Southern blotting, a particular kappa (kappa) L chain variable region (V) probe was recently found to hybridize to Vkappa cDNA from CSF B cells from almost one half of the MS patients tested but only 10% of normal or other neurologic disease controls [Zhou, S.-R., Maier, C.C., Mitchell, G.W., LaGanke, C.C., Blalock, J.E., Whitaker, J.N., 1998. A cross-reactive idiotope in cerebrospinal fluid cells in multiple sclerosis: further evidence for the role of myelin basic protein. Neurology 50, 411-417.] Here, we report that this likely results from remarkable sequence similarity in certain Vkappa from CSF B cells from different individuals with MS. The high degree of sequence homology even extended to all three complementarity determining regions (CDR) which in part form an antibody combining site. In addition, marked sequence homology was observed between the light chains from the MS patients and those from certain mouse antibodies against myelin basic protein (MBP). The results establish, in principle, that the same or very similar kappa light chain variable regions can be shared between CSF B lymphocytes from different individuals with MS as well as with certain antibodies against MBP.