Clinical, haematological, biochemical, bacteriological, histological, and immunological data in 300 patients with ulcerative colitis have been examined with special reference to liver disease and dysfunction. Biochemical dysfunction of the liver is common. Forty-five patients (15 per cent) had an abnormality of one or more of the three basic tests of liver dysfunction used in this study: the bromsulphthalein retention test, the serum glutamate pyruvate transaminase, and the alkaline phosphatase. Further biochemical tests contributed little additional information. A considerable proportion of patients with biochemical liver dysfunction had no histological abnormality in biopsy material. Conversely, a number of patients with normal biochemical findings had pathological changes in liver biopsy specimens. In almost all patients in this group the pathological changes were of a minor nature. Thirty-one patients (10-3 per cent) had one or more pathological changes in their liver biopsy specimens. Fatty change was the commonest occurring in 19 patients (6·3 per cent); and it was the principal change in 14 (4·7 per cent). Pericholangitis occurred in 15 patients (5 per cent) and was the principal finding in 12 (4 per cent). Chronic liver disease was infrequent and occurred in only four patients (1·3 per cent); three patients with post-necrotic cirrhosis and one patient with chronic active hepatitis. One patient had severe amyloid infiltration of the liver. Culture of liver tissue for bacteria and L forms was negative. Immunological tests showed a number of patients with a positive immuno-fluorescent test for human colon (25 patients or 12·7 per cent) and for antinuclear factor (8·9 per cent). Tests for thyroglobulin antibodies were positive in 29 patients (10·8 per cent). No relationship was found between hepatic lesions and any of the positive immunological tests. Immunoglobulin assay did not show striving changes in those patients with liver disease or dysfunction. In ulcerative colitis, minor pathological changes in the liver are more frequent than overt chronic liver disease. The present type of study almost certainly underestimates the frequency of major liver disease in ulcerative colitis because this particular combination carried a poor prognosis. The question of whether pericho-langitis is the common precursor of post-necrotic cirrhosis cannot be answered at present, but the data now available will provide the solution if the same patients are kept under observation for a number of years. The aetiology of the hepatic lesions remains obscure but some deductions can be drawn from the present data. From clinical considerations, the overt liver disease appears to behave like a viral hepatitis which has become chronic. There is no evidence to support the view that homologous serum hepatitis from blood transfusion is the significant factor. Drugs do not appear to be of any great relevance. Immunological relationships are essentially negative. Portal bacteraemia appears to be an unlikely cause of the overt chronic liver disease encountered in the present study.