The need for standardization of methods for the control of anticoagulant therapy was apparent 25 years ago. With the development of the ratio method for comparing the sensitivity of different thromboplastin preparations it became possible to equate the value obtained with one preparation in terms of the value which would be obtained with any other preparation, and the need for a reference to serve as a yardstick for comparison became obvious. The first trial reference preparation was developed in 1965 and three small international trials on the calibration of different thromboplastin preparations were conducted. The first international reference preparation was laid down in 1967 coded 67/40, and other preparations containing ox brain, human brain and rabbit brain and coded 68/434, 69/223 and 70/178 followed. Further collaborative studies were carried out in 1970 and 1973, and a large international trial undertaken in 1974, using 70/178 as the reference preparation. These preparations have remained stable over a period of 9 to 12 years and their usefulness for purposes of calibration and international trials has been proven. Three further reference preparations were laid down in 1979 and a further international collaborative study has been undertaken.