Histones are frequent targets of self-reactive antibodies during autoimmune syndromes. We report the specificities and V region genes of three IgG anti-histone MAbs obtained from autoimmune mice. Each of the MAbs, named LG2-1, LG2-2 and BWA3, is directed against a different determinant located in the basic amino-terminal domain of core histones. LG2-1 reacts with a peptide from histone H3 (residues 30–45), LG2-2 recognizes the amino-terminus of H2B (residues 1–13) and BWA3 binds an epitope corresponding to a region of high sequence similarity between H2A and H4 (residues 1–20 and 1–29, respectively). The analysis of their V region sequences indicates that the H chain CDRs of these MAbs are remarkable for the presence of negatively charged amino acid residues that may play a role in the binding to cationic histones. The H chain importance in conferring reactivity to histones is corroborated by the observation that each of the V_H gene segments of these MAbs is very similar to V_H genes of previously described murine anti-histone antibodies.