Anti-GM1 antibodies have been implicated in the pathogenesis of several neurological diseases, but the role of these antibodies is still controversial. An animal model could provide insight into the mechanisms of these human disorders, but obtaining specific anti-GM1 monoclonal antibodies (mAbs) has been extremely difficult because of the weak immunogenicity of GM1 ganglioside. Four murine mAbs against GM1 were elicited by immunization of mice with lyso GM1 coupled to BSA and GM1 glycolipid. All four IgM,k mAbs bound strongly to GM1, three antibodies (125, 360 and 494) also bound very weakly to asialo GM1 (GA1) and one (156) bound weakly to GD1b. Three antibodies (125, 360 and 494) were encoded by the same VH and V kappa genes. The VH gene exhibited 97% homology to VHOX1, a member of the VHQ52N gene family, the D segment was probably derived from DQ52 and JH was identical to JH2. The V kappa gene was approximately 99% homologous to V kappa RF and J kappa was germline J kappa 2. The VH gene of mAb 156 exhibited 98% homology to VH205.12, of the VHJ558 gene family, the D segment was derived from DFL16.1, and JH was germline JH2. The V kappa and J kappa genes of mAb were identical to V kappa 8 and J kappa 1, respectively. The genes encoding these anti-GM1 antibodies were close to germline sequences and have been used to encode other antibodies. This suggests that the unresponsiveness of mice to immunization is probably due to inactivation of self-reactive B cells. These rare anti-GM1 mAbs will be valuable reagents for studies of the pathogenesis of autoimmune neuropathy in animals, and also for analyzing the tissue distribution and functions of GM1.