To elucidate the safety of fibrin glue application, antibody formation against fibrinogen and thrombin was studied in rabbits. The pathophysiology of developed antibodies was tested by an intravenous challenge with both components and by related blood pressure measurements. All fibrin glue-treated animals developed antibodies against both components. The quantity of antibodies against thrombin (20.4 mg/mL) was higher than the quantity against fibrinogen (0.38 mg/mL). The intravenous challenge with both components resulted in a significant and long-lasting blood pressure decrease to about 50% of the control values, indicating that these antibodies can induce circulatory disorders by antigen-antibody reaction, activation of the complement cascade, and liberation of histamine. Since rabbits promptly produce antibodies against antigenic material and humans do not, the results of this investigation suggest that fibrin glue should be used with caution in humans.