The natural history of primary sclerosing cholangitis (PSC) is poorly defined and its management remains controversial. Forty-eight symptomatic patients (median age 39 years, range 8-67 years; 30 male) with PSC were reviewed retrospectively. Thirty patients had inflammatory bowel disease. Four patients (8 per cent) developed or had an associated malignancy. Twenty-one (44 per cent) died; overall 5 year actuarial survival was 30 per cent. Twenty-three patients had 27 non-transplant related biliary operations (16 patients specifically for PSC) of whom 12 died. Serum bilirubin was the only parameter to improve after biliary surgery. Seventeen patients (35 per cent) underwent orthotopic liver transplanation (OLT) of whom nine are currently alive (1 year projected survival of 55 per cent). Previous biliary surgery correlated with a poor outcome (P < 0.0001) after OLT. Being male, presence of cirrhosis, duration of symptomatic disease (> 3 years) and a serum bilirubin level > 100 μmol/l at presentation, were independently associated with a poor outcome (P < 0.05). These data provide evidence that PSC is a progressive disease and conventional surgical options have little influence on the outcome. Previous biliary surgery adversely affects outcome following OLT. For progressive liver disease, liver transplantation should be considered the treatment of choice.