Severe familial factor V:C deficiency is a rare, recessively inherited coagulation disorder but there is little information in respect of the accuracy and reliability of factor V:C assays that are required for diagnosis and treatment monitoring. We present here the results of three External Quality Assessment exercises in respect of factor V:C assays undertaken by 192--225 participating laboratories performed over a 2-year period. Consistent significant differences were observed between results obtained using different reference plasmas and different thromboplastins. The relationship between results obtained with different reference plasmas was not constant and varied between the surveys. In-house studies confirmed the observation derived from the External Quality Assessment surveys that the choice of commercial reference plasma significantly affects the results of factor V:C assays. These results clearly indicate the necessity for an international standard for factor V:C.