Enzyme-linked immunosorbent assay (ELISA) and immunoblotting were used to define comparatively the frequency of antibodies to total histones and different histone fractions - H1, H2A, H2B, H3, and H4 - in 16 patients with idiopathic systemic lupus erythematosus. H1 and H2B showed the most prominent antigenic properties; H3's were weaker, while antibodies to H2A and H4 were rarely detected and only with the more sensitive ELISA on microtiter plates. Detailed specification was carried out of the antigenic determinant on fragments obtained by specific cleavage of purified H1 at phenylalanine-106. Antibodies were detected against both the NH2 and COOH terminal halves of the molecule. The presence of antihistone antibodies was not associated with any particular clinical symptoms, but an obvious link with disease activity has been proved.