In order to determine the value of serum bile acids in predicting the course of chronic cholestatic liver diseases, we measured individual serum bile acids serially, using high-performance liquid chromatography, over a 4 year observation period in 12 patients with primary biliary cirrhosis and six patients with primary sclerosing cholangitis. The changes in individual serum bile acids and the ratios thereof, conventional liver tests and Child-Turcotte and Mayo scores were compared between survivors (n = 10) and patients who underwent liver transplantation for (n = 3) or died of the liver disease (n = 5). Patients with a serum total chenodeoxycholic acid concentration at study entry that exceded 15 mumol/L were 10 times more likely to die or need a liver transplant in the following 4 years than those with chenodeoxycholic acid levels < 15 mumol/L (P < 0.05). None of the other biochemical parameters or clinicopathological scores could similarly discriminate between the two groups at entry. Time-dependent analyses for the cholic acid/chenodeoxycholic acid ratio, serum total bilirubin and albumin concentrations and Child-Turcotte and Mayo scores were able to differentiate between primary sclerosing cholangitis patients who died or were transplanted and those who were not, whereas age of the patients and other parameters did not. The taurocholic acid/taurochenodeoxycholic acid ratio fell during progression of primary biliary cirrhosis but rose in temporal relationship with primary sclerosing cholangitis. This differential pattern of change was unique compared with other clinical and laboratory indices. In conclusion, serum chenodeoxycholic acid levels and the cholic acid/chenodeoxycholic acid ratio in both diseases were independent indices that allowed for the prediction of survival or the need for liver transplantation. These indices are worthy of further examination in a larger group of patients as prognostic criteria for chronic cholestatic liver disease and in the assessment of the efficacy of therapeutic interventions, including liver transplantations.