A case-control study of fibrinolytic activity was conducted comparing 12 women with a recent history of thromboembolism while taking oral contraceptives and 28 matched female controls without a history of thromboembolism. All subjects had stopped using oral contraceptives at least 12 months prior to study. A new assay, recently developed in this laboratory, was used to evaluate the mean fibrinolytic response to venous occlusion in both cases and controls. The fibrinolytic response of all subjects was stratified into quartiles as previously described. While the controls segregated as expected, all 12 cases occurred in subjects whose fibrinolytic response fell in the first two quartiles with 8 of the 12 subjects having first quartile responses. The mean fibrinolytic response for all controls was 12.3 units while cases showed a mean response of only 3.9 units. The above data supports and extends our recent suggestion that low fibrinolytic response may signal a natural predisposition to venous thromboembolism which could be triggered by use of synthetic estrogens. However, these data do not support the use of this assay as a screening test for oral contraceptive related risk to thromboembolism since at least 50% of the control population also segregate in the first two quarters.