We studied the sensitivity of various animal plasmas to activated human protein C (APC) and found an impaired response in the order monkey < horse < pig < dog < rabbit. We assume that this effect was mainly caused by differences in the APC cleavage region of factor V, as recently described for the factor V Leiden mutation in humans. In APC-dependent assays, which are based on the inactivation of factor Va, 5% (v/v) rabbit plasma added to human plasma mimicked the APC response seen in heterozygous carriers of factor V Leiden; 20% rabbit plasma gave results similar to those seen in homozygotes. We exploited this factor V Leiden-like behaviour to prepare plasma standards for calibration of APC-dependent assays by mixing rabbit and human plasmas. The 0% value was assigned to the clotting time in the absence of APC, while the 100% value was assigned to the clotting time in presence of APC. A normal human plasma pool was used as reference. These standards were used to establish reference curves. On automated coagulation analyzers, the results obtained were automatically reported as 'percent normal'. This not only simplified evaluation, but also improved the comparability of results.