Monoclonal antibodies to bacterial lipopolysaccharide (LPS) were prepared by fusing spleen cells from BALB/c mice immunized with Salmonella Minnesota Re 595 LPS to the mouse myeloma cell line P3U1. One of them, designated RS01, revealed a strong positive antinuclear activity and reacted with DNA-histone. RS01 also bound specifically to Salmonella Minnesota Re 595 LPS and eliminated the biological activity of LPS. The Salmonella completely inhibited the ANA activity of RS01 and DNA-histone blocked the reactivity of RS01 with LPS. Thus, it is clear that an anti-LPS monoclonal antibody, RS01 cross-reacts with DNA-histone.