Fifty sera which gave ring-like nuclear staining in immunofluorescence on rat liver tissue sections were characterized. Using immunoprecipitation and Western blotting we showed that 10 of the sera contained antibodies to 200 kD polypeptide(s) of nuclear envelope. Clinical and biological data were available for nine of the patients. Strikingly, all of these patients suffered from primary biliary cirrhosis with eight of them having anti-mitochondrial antibodies. As no control serum displayed such a reactivity, anti-200 kD polypeptide(s) antibodies can be considered as a new marker specific of a subset of primary biliary cirrhosis, being present even when anti-mitochondrial antibodies are absent. The exact identity of the target remains to be established, since several polypeptides of similar molecular weight have been reported to belong to the nuclear envelope.