Recent investigations have clarified the clinical, radiologic, and pathologic features of primary sclerosing cholangitis, a chronic fibrosing disorder affecting the biliary tree. This progressive, cholestatic biliary disease is diagnosed when an elevated serum alkaline phosphatase level and stricturing and beading of bile ducts on cholangiography are found in a patient with jaundice, bouts of cholangitis, and, frequently, ulcerative colitis. The disease results in a spectrum of hepatic changes characterized by periductal and portal fibrosis, bile ductular proliferation, diminished numbers of normal bile ducts, piecemeal necrosis, and copper accumulation. The clinicopathologic features of primary sclerosing cholangitis, hypotheses on its pathogenesis, and possible forms of therapy are examined.