Seventy-six patients with clinically and histologically defined primary biliary cirrhosis, who were in stage I/II at the time of first diagnosis and could be followed for 6-18 years (mean 10 years), were analysed with respect to their clinical course. Forty-four of the 76 patients remained in stage I/II during the observation period (group 1), while 32 progressed to late stages (group 2). Sera of these patients were retested for anti-M2, anti-M4, anti-M8 and anti-M9 antibodies by ELISA and the complement fixation test (CFT). Four different AMA-profiles A-D could be differentiated in these patients: profile A, only anti-M9 positive by ELISA; B, anti-M9 and/or anti-M2 positive by ELISA; C, anti-M2, anti-M4 and/or anti-M8 positive by ELISA; and D, anti-M2, anti-M4 and/or anti-M8 positive by ELISA and CFT. When the natural courses of patients and the four different AMA-profiles were compared retrospectively it became evident that 97% of group 2 patients already had the AMA-profile C/D at entry into the study. Of the patients in group 1 70% had the AMA-profile A/B. Increases in bilirubin levels during the course of the disease were observed preferentially in patients of group 2 (profile C/D). We conclude that the determination of AMA-profiles in PBC patients is a sensitive approach for the early prediction of the outcome of the disease.