The incorporation of gentamycin, neomycin and Polymyxin E into fibrin seal results in prolonged clotting time after mixture with 4 NIH-units of thrombin per ml in vitro. The aminoglycoside antibiotics gentamycin and neomycin also diminished fibrin-alpha-chain crosslinkage and, as a consequence, clot rigidity, as demonstrated with clots containing gentamycin. Clotting time and the rate of alpha-chain crosslinking can be adjusted to normal values by the use of higher thrombin concentrations and incorporation of additional factor XIII into the sealing system. Drug release from the clots was similar for all three antibiotics tested and mainly dependent on the concentration gradient between the clot and its environment. Under the conditions of the present study, about 85% of the antibiotic content of fibrin seal clots were released within 72 h.