This report describes the identification of autoantibodies that react with c-myc proteins in the sera of some patients with autoimmune diseases. Sera from nine to 30 patients, including six with systemic lupus erythematosus, one with mixed connective tissue disease, one with dermatomyositis and one with autoimmune haemolytic anaemia, reacted in immunoblotting assays against a truncated human c-myc protein p42 produced by Escherichia coli. Furthermore, these sera exhibited double bands of 58,000 and 60,000 MW in the nuclear fraction of HL-60 cells with the amplified c-myc gene. These bands were the same as those detected by the anti-human c-myc protein monoclonal antibody (MYC-1) by immunoblotting assay. The binding activities to 58,000 and 60,000 MW were not reduced by DNase I digestion with the sera and could be absorbed by a p42-bound affinity column and recovered after elution.