Neuropathogenic murine antibodies reactive with terminal disialylgalactose epitopes are innate and preferentially encoded by the VH7183.3b gene. Here we have studied antibodies reactive with internal galactose-linked disialosyl epitopes and the terminal trisaccharide of GT1b. Antibodies were of moderate affinity and unmutated. Anti-GD1b antibodies were often encoded by the VH10.2b heavy and gj38c light chain genes. Anti-GT1b antibodies with broader glycan binding patterns were encoded by VHQ52 and VHJ558 family genes. These data indicate that the discrete specificities of ganglioside-binding antibodies are dictated by particular patterns of V gene usage residing within the innate B cell repertoire.