MRL/1 mice develop a severe form of systemic lupus erythematosus and spontaneously produce high levels of autoantibodies to DNA. Spleen cells from these animals were used as fusion partners to prepare hybridomas that produce autoantibodies to DNA. Since exogenous immunization was not employed, the hybridoma antibodies were derived from populations of B cells that spontaneously produced autoantibodies. Each hybridoma autoantibody had a distinctive binding specificity with S-DNA, N-DNA, or oligonucleotides.