Anti-ENA antibodies have been found in 176 sera which nearly all contained antinuclear antibodies giving a speckled pattern of nuclear fluorescence. The charts of 134 of these 176 patients were available for a thorough clinical study. Among these 134 patients, 59 had a well defined Connective Tissue Disease including 40 SLE, 31 had a limited clinical syndrome made of Raynaud's phenomenon, inflammatory polyarthritis, swollen fingers and hyperglobulinemia and 34 had a complex clinical picture associating signs of more than one connective tissue disease. Some of the patients in this third group could be considered as-having the Mixed Connective Tissue Disease (MCTD) described by Sharp et al. Anti-RNP antibodies were more common in this series than the other anti-ENA antibodies. However, no narrow specificity could be assigned to any of these antibodies. This is true of the non anti-RNP antibodies, the anti-Sm in particular, which were found in 49 patients of whom 32 had SLE existing alone or in association with features of other connective tissue diseases and 17 had another connective tissue disease or the afore-mentioned limited clinical syndrome. In any case, the anti-ECT antibodies never reach the diagnostic value of the anti-DNA antibodies.