Routine laboratory tests are of little help for early detection and differential diagnosis of hepatic dysfunction following orthotopic liver transplantation (OLT). In the present study, serum levels of esterified bilirubin, total bilirubin and bile acids were investigated in 20 patients after OLT. Twenty episodes of liver dysfunction were observed: 10 rejection episodes, 3 cases of thrombosis of the hepatic artery, 3 cases of septic shock, and 4 episodes of cyclosporin toxicity. During rejection, the median increase in esterified bilirubin was 3.2-fold (range 1.6-24.9), while total bilirubin increased 1.5-fold (range 0.7-3.4). Bile acids increased 3.6-fold (range 2.5-6.6; peak levels 25-87 microM). Both bile acids and esterified bilirubin increased 1-3 days earlier than serum transaminases and decreased only after successful anti-rejection treatment. The response of bile acids to successful treatment was usually more rapid than the response of esterified bilirubin. Hepatic artery thrombosis and septic shock were associated with a sharp increase in esterified bilirubin and very high bile acid levels (peak levels 80-185 microM). During cyclosporin toxicity, a characteristic pattern of progressively increasing bilirubin with no change in the bile acid levels was observed. Both esterified bilirubin and bile acids are very sensitive indicators of hepatic graft dysfunction. In particular, serum bile acids are useful for identifying cyclosporin toxicity and monitoring the response to anti-rejection treatment.