Mice of the strain MRL/Mp-lpr/lpr develop a lupus erythematosus-like syndrome that includes the production of autoantibodies specific for nucleic acid-containing cellular components. We have fused spleen cells from such a mouse with the myeloma SP 2/0 and examined the antibodies produced by the resultant cloned hybrid cell lines by using immunoprecipitation and immunofluorescence techniques. Three types of monoclonal antibodies, specific for Sm, DNA, or rRNA, all antigens to which patients who have lupus make antibodies, have been identified. Patient anti-Sm antibody had previously been reported to precipitate five small nuclear ribonucleoproteins that contain U-1, U-2, U-4, U-5, and U-6 RNAs. The monoclonal anti-Sm antibody gives the same immunoprecipitation pattern, providing direct evidence that the Sm antigen resides on all these RNA-protein complexes. Monoclonal anti-Sm antibody will be valuable in deciphering the biological function of these ubiquitous small nuclear RNPs. A simple competition radioimmunoassay using the monoclonal anti-Sm antibody to titer patient sera is also presented. Uses of monoclonal antibodies for the study of autoimmune disease are discussed.The sera of patients and mice that have autoimmune disorders contain antibodies whose presence often results in tissue injury. The mechanisms leading to the development of autoantibodies are not well understood. However, the appearance of specific antibodies in patient sera has been reported to be associated with particular clinical signs of disease (1). Studies with monoclonal antibodies having the same specificity as such autoantibodies could result in a clearer understanding ofboth the mechanisms leading to the formation of autoantibodies and the role of such antibodies in producing disease. Mouse monoclonal antibodies to DNA and ribosomal RNA have been described (2, 3).Autoantibodies also provide potent tools to probe the structure and function ofthe cellular constituents against which they are directed. We have previously used antibodies from the sera of patients who have systemic lupus erythematosus (SLE) to examine the antigens designated Sm, RNP, La, and Ro (4-6). Each of these antigens resides on discrete particles composed of RNA and protein and called either small nuclear ribonucleoproteins (snRNPs) or small cytoplasmic ribonucleoproteins.Anti-Sm has been found to precipitate five different snRNPs, containing the small RNAs U-1, U-2, U-4, U-5, and U-6, from mammalian cell extracts. One snRNP that bears the RNP as well as the Sm determinant appears to be involved in the nuclear splicing of mRNA precursors (7), while cellular roles for the Laand remaining Sm-bearing snRNPs and for the Ro-containing small cytoplasmic RNPs are unknown. The availability of monoclonal antibodies directed against snRNPs would eliminate many uncertainties in experimental interpretation raised by the use of patient sera.Antibodies to Sm are found in certain SLE patients (1), dogs with a lupus-like syndrome (8), and the MRL/Mp-lpr/lpr (MRL/1) and MRL/M...