Eighty-two patients with systemic lupus erythematosus (SLE) were investigated for the presence and significance of serum antibodies to Extractable Nuclear Antigen (ENA) and its major components, RNP, Sm and SS-B (or Ha). The counterimmunoelectrophoresis assay allowed independent detection and measurement of antibodies to the different components. Forty patients had anti-ENA antibodies, 25 (30% were of anti-RNP type alone or anti-RNP associated with anti-Sm, and 12 (15% were of anti-RNP type alone. Anti-ENA antibodies distinguished a subset of patients with less common incidence of renal disease, positive Coombs test, anticoagulant serum factors and high titres of anti-DNAds antibodies, with higher incidence of Raynaud's phenomenon, swollen hands, hypergammaglobulinemia and high titres of antinuclear antibodies with speckled pattern on immunofluorescence. SLE patients with anti-RNP antibodies had in addition a high frequency of normal complement values. All but one SLE patient with only anti-RNP antibodies fulfilled at least four or more criteria for the diagnosis of SLE. We conclude that anti-ENA antibodies in SLE patients are associated with a low prevalence of nephritis and a clinical and laboratory profile similar to that of the MCTD syndrome. These findings demonstrate the difficulty of inferring rigid differences between MCTD and SLE. The MCTD syndrome probably represents only one segment of the whole clinical spectrum of SLE. © 1984 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.