400 mg/dl) and in plasma from anticoagulated patients. The systematic overestimate in the latter samples could be a result of an increased fibrin gel turbidity, as shown by in-vitro experiments using purified fibrinogen clotted by different thrombin concentrations. The PFC overestimate by the prothrombin-time-derived method could also be experimentally reproduced by competitively inhibiting thrombin–fibrinogen interaction by hirudin 54–65 peptide and the fibrinogen fragment E. A similar qualitative result was also found for the prothrombin-time-derived method in the presence of the Gly-Pro-Arg-Pro peptide, which competitively inhibits the end-to-end fibrin aggregation process. Notably, under both the above experimental conditions, the Clauss method underestimated the PFC. On the other hand, the 'clot recovery' method was minimally affected by the above inhibitors. These results indicate that the prothrombin-time-derived method is accurate and precise for most routine purposes. Its precision seems inadequate, however, under those conditions where the prothrombin time is prolonged (such as anticoagulant therapy) and in the presence of high fibrinogen levels.