To assess the prevalence and significance of chronic ulcerative colitis in patients with severe autoimmune hepatitis and to determine the frequency of cholangiographic and histologic features of primary sclerosing cholangitis in those with colitis, 105 patients who had been screened by annual proctoscopic examination were studied. Patients with features of colitis were compared to counterparts without colitis who had been matched by age, sex, disease severity and treatment regimen. Seventeen patients (16%) had findings of chronic ulcerative colitis. Twelve of these underwent cholangiography and five (42%) had features of primary sclerosing cholangitis. Patients with and without cholangiographic abnormalities were indistinguishable by clinical, laboratory, immunoserologic, and histologic features. Fibrous obliterative cholangitis was present in only two patients, including one with normal cholangiography. Patients with colitis entered remission less frequently (59 vs. 94%, p less than 0.05), failed treatment more commonly (41 vs. 6%, p less than 0.05) and progressed to cirrhosis more frequently (75 vs. 25%, p less than 0.05) than counterparts without colitis. Patients with colitis but normal cholangiography, however, responded satisfactorily to therapy. We conclude that chronic ulcerative colitis can coexist with severe autoimmune hepatitis in the absence of primary sclerosing cholangitis or hepatitis C infection. Under such circumstances its presence does not adversely influence treatment outcome. Primary sclerosing cholangitis cannot be excluded by routine examinations and its presence is associated with a poor treatment response. Cholangiography should be considered in all patients with autoimmune hepatitis and colitis, especially in those recalcitrant to therapy.