PIP: Oral contraceptives, currently used by about 54 million women worldwide, have been associated with thrombotic disease. Possible mechanisms of thrombosis due to the Pill are: 1) the blood coagulation system; 2) plasma inhibitors of blood coagulation, particularly antithrombin 3; and 3) proteins involved in fibrinolysis, e.g., plasminogen and plasminogen activator. The Pill may also either induce abnormal findings or aggravate preexisting defects. The author and his colleagues studied the fibrinolytic system in 15 Pill users (12 with pulmonary embolic and deep vein/superficial vein thrombosis, and 3 patients with arterial thrombosis) and 29 controls. Blood samples were collected at 2 different periods (preocclusion and postocclusion) and assayed for plasminogen activator. The figure obtained when preocclusion values of activator are subtracted from postocclusion values is called releasable plasminogen activator (RPA). Almost 90% of Pill users who had thromboembolism had between 2 to 8 units of RPA, the lowest end of the distribution. 38% of normal subjects exhibited values within this range. Statistical analysis reveals that a low RPA level is 6 times more likely to occur in pill users with thromboembolic events than in normal women. In this study, the strongest association between low RPA and thromboembolism occured in those with venous thromboembolism. Other studies have reported on the correlation between low RPA and increased risk of myocardial infarcts, ischemic cerebrovascular disease, and deep-vein thrombosis. The author developed a more sensitive and reliable radioassay for RPA and used it to reexamine the 12 women who had venous thromboembolism and 28 of the original controls. Dividing the range of RPA into quartiles resulted in the clustering of 12 cases in the lowest 2 quartiles, with 75% of the subjects in the lowest quartile. The data were highly significant (p.001). It is suggested that both RPA levels and antithrombin 3 activity be measured in women before they start taking the Pill and again 3 months later. Those with an RPA unit of less than 1 and an antithrombin 3 level of under 75% should not take the Pill. The value of exercise in reducing the risk of thrombotic disorders is indicated.