An antinuclear immunofluorescence pattern displaying a thin ring confined to the nuclear envelope was assessed in sera from 38 patients with primary biliary cirrhosis and in sera from a control group of 277 patients with other antinuclear antibody-positive diseases. This rim-like antinuclear reactivity was present in sera from 20 primary biliary cirrhosis patients (52.6%) but in only two patients from the control group (0.7%) (p less than 0.001). Furthermore, this autoantibody was present in three of four primary biliary cirrhosis patients without antimitochondrial antibodies. Presence of this rim-like pattern in primary biliary cirrhosis did not correlate with the presence of associated autoimmune diseases nor with other clinical, biochemical, nor histological features of the disease. The antigenic specificity of sera displaying this antinuclear immunofluorescence pattern was characterized by Western blot analysis using an antigenic extract containing nuclear envelope proteins purified from rat liver. Sixteen of the 20 positive sera showed a common pattern of reactivity with a set of nuclear envelope-associated proteins approximately 200 kD in size. In conclusion, sera from primary biliary cirrhosis patients showing a rim-like fluorescent nuclear pattern have antinuclear autoantibodies that react specifically with components of the nuclear envelope. The high specificity of these new autoantibodies in primary biliary cirrhosis indicate that they might be a serological marker of the disease, particularly useful in patients without antimitochondrial antibodies.