The clinical and serologic features of 7 patients whose sera contained antibodies directed against proliferating cell nuclear antigen (anti-PCNA) were studied. Five of the patients had systemic lupus erythematosus (SLE), 1 had idiopathic diffuse proliferative glomerulonephritis, and 1 had seronegative arthritis. In a study of various rheumatic diseases, anti-PCNA was found in 2% of SLE sera but was not found in the sera of 100 rheumatoid arthritis patients, 20 mixed connective tissue disease patients, or 50 diffuse scleroderma patients. Patients with anti-PCNA had no history of hemolytic anemia, leukopenia, thrombocytopenia, or pleuro-pericarditis. Evidence that the production of anti-PCNA antibodies is sensitive to corticosteroid therapy is also presented.