In a 15-year surveillance program for long-standing, total ulcerative colitis (UC), 72 patients were followed up with colonoscopic biopsies. Seventeen patients developed definite dysplasia, carcinoma, and/or DNA aneuploidy. Alkaline phosphatase and transaminases were examined in all patients. In the group with dysplasia, carcinoma, and/or DNA aneuploidy, 5 patients (28%) were found to have primary sclerosing cholangitis (PSC) based on histological and/or cholangiographic criteria. In the group without definite dysplasia or DNA aneuploidy, no patient with PSC appeared, although two patients with other forms of chronic liver disorders were found. The difference in distribution of PSC between the two groups was statistically significant (P = 0.0004). Using logistic regression, the presence of PSC and the duration of UC were identified as independent risk factors associated with dysplasia and/or DNA aneuploidy. Thus, UC patients with PSC seem to run an increased risk of developing colonic dysplasia and/or DNA aneuploidy. Although the reason for the increased risk is still unclear, these results warrant increased surveillance among patients with both PSC and longstanding, total UC.