Three hundred eighty-two patients who underwent major operations for gynecologic malignancy were studied prospectively to determine the natural history of postoperative venous thromboemboli. Iodine 125-labeled fibrinogen leg counting, to diagnose deep venous thrombosis, was performed daily. Sixty-three patients (17%) developed postoperative venous thromboembolic complications. Deep venous thrombosis initially arose in the calf veins in 52 patients. Twenty-seven percent of these thrombi lysed spontaneously. Four percent of thrombi in the calf veins progressed to deep venous thrombosis in the femoral vein, and 4% resulted in pulmonary emboli. Nine other patients developed proximal deep venous thrombosis without prior thrombosis in the calf veins. One patient with proximal deep venous thrombosis also had a pulmonary embolus. Two patients with no evidence of deep venous thrombosis on prospective 125I-labeled fibrinogen leg counting developed pulmonary emboli, including one fatal pulmonary embolus that was found at autopsy to have arisen from the internal iliac veins. Fifty percent of all venous thromboemboli were detected within 48 hours of operation, although two patients developed significant deep venous thrombosis and pulmonary emboli after discharge from the hospital. These results add important information to our understanding of this disease process, and raise issues related to appropriate treatment and prophylaxis of venous thromboembolism in patients after gynecologic operations.