The mechanism and significance of elevated levels of serum fibrin degradation products (FDP) in pulmonary embolism were investigated experimentally. Dogs were embolized with autologous blood clot-incorporating canine 125I-fibrin and were infused with either saline, heparin, or streptokinase. Serial measurements were made of total FDP by hemagglutination inhibition assay and of radioactive FDP. After saline, the peak level of total FDP was 323 mug/ml, but radioactive FDP was only 8 mug/ml. After heparin, these values were 44 and 11 mug/ml, respectively, and after streptokinase, 415 and 20 mug/ml. The results suggest that under these experimental conditions the elevated levels of FDP in pulmonary embolism are derived mainly from lysis of fibrin deposited after embolization rather than from lysis of the original embolus. Heparin inhibits both fibrin deposition and elevation of FDP levels after embolism.