ABSTRACT— Clinical, biochemical and serological data obtained in 103 patients with primary biliary cirrhosis (PBC) were analysed with respect to the four defined morphological stages. Evaluation of the initial biopsies (99 needle biopsies/4 wedge biopsies) revealed that most patients were in stage I (focal bile duct destruction). Unequivocal distinction between stages I and II was possible in most cases, while considerable overlapping of criteria was observed in stages II to IV. Morphological cholestasis, a characteristic sign of stage IV was already found in 7% of PBC I cases. Four out of 12 autopsy specimens showed micronodular biliary cirrhosis (Hanot's type) and eight specimens had a macronodular type of biliary cirrhosis. No predominant clinical symptoms were found in patients with PBC I or II, but pruritus was observed in about 30%. Increased serum alkaline phosphatase (AP) and IgM levels as well as a positive antimitochondrial antibody (AMA) test were typical features of all stages in up to 80–90%, but patients with normal AP or IgM or negative AMA have been observed, especially in stages I and II. Five of 57 patients at stage I had increased bilirubin levels and in three patients IgM and IgG were simultaneously elevated in stage I. The natural course of PBC, as it is reflected in histological staging, was studied in 30 patients in whom biopsies were regularly taken over a period of 2–18 years. About 80% of PBC I-cases lasted between 1 and 7 years before reaching stage II, while another 5–10 years were necessary for the development of stage III-IV. Thus it appears that in the vast majority of patients PBC lasts about 10–15 years and in some instances even more than 20 years. The finding in stage I and II of normal AP indicates a benign course, while morphological and biochemical cholestasis seems to be associated with a rather progressive course.