The authors report the clinical and liver biopsy features of nine patients with primary autoimmune cholangitis, a unique form of chronic nonsuppurative destructive cholangitis associated with high-titer serum antinuclear antibodies, including eight women and one man; their median age was 51 years. All patients showed cholestatic hepatic enzyme profiles (median gamma glutamyl transferase and alkaline phosphatase, 800 U/L and 700 U/L, respectively). The median antinuclear antibody titer was 1:1,280 (range, 1:640–1:2,560). All patients' sera were negative for antimitochondrial antibodies; six were also nonreac-tive for anti-M2 mitochondrial autoantigens. Liver biopsies showed marked paucity of interlobular bile ducts (median percentage of portal tracts containing bile ducts, 11%; range, 0–50%). Granulomatous cholangitis was present in two cases; five livers showed the pattern of bile ductular proliferative piecemeal necrosis. Seven patients were treated with prednisone and azathioprine without clinical benefit. During follow-up of 1 to 5 years, disease has progressed in seven patients, including four who have developed other autoimmune conditions. Although clinically, biochemically, and histopathologically comparable to primary biliary cirrhosis, autoimmune cholangitis abdicates antimitochondrial antibodies in favor of antinuclear antibodies. It represents a distinctive subset of antimitochondrial antibody-negative adult ductopenic disorders, for which conventional immunosuppressive therapy does not appear warranted.