Irreversible initial non-function of the graft liver is a life-threatening early complication of orthotopic liver transplantation (OLT), which needs immediate retransplantation if the patient is to survive. Since protein C (PC) is a vitamin K dependent protein synthesized in the liver and with the same half-life as factor VII (FVII), the behaviour of PC in patients undergoing OLT was studied in comparison with prothrombin time (PT) and FVII. Twelve OLT patients were divided into two groups on the basis of clinical outcome: group A (six cases) in which OLT was successful, and group B (six cases) who developed initial non-function of the graft liver. PT, FVII activity (FVII:act) and antigen (FVII:Ag) and PC activity (PC:act) and antigen (PC:Ag) were carried out on six blood samples collected during the operation. At baseline, coagulation disorders were in agreement with the underlying liver disease, but no differences were seen between the two groups when all tests were considered. Ten minutes, 1, 2 and 3h after liver graft reperfusion, mean PT and FVII:act were always significantly increased in good responder patients compared to non-responders. FVII:Ag and PC:Ag were significantly higher in group A than in group B starting 2 h after the liver graft reperfusion; no difference was seen in PC:act levels between the two groups. In addition, PC:Ag mean levels were increased with respect to corresponding PC:act values in non-responder patients, suggesting a qualitative rather than quantitative defect of protein synthesis due toliver damage. In conclusion, PT and FVII:act were more sensitive than PC activity as early prognostic indices of clinical out come in OLT.