Sulfamylon (mafenide) solution, a potent experimental topical antimicrobial, is used in our burn unit to treat burn wounds both before and after skin grafting. The importance of fibrin to early graft adherence prompted this in vitro study of the effect of Sulfamylon upon fibrin clot. Assessing fibrinolysis by in vitro proteolysis of [125I] fibrin monomers, Sulfamylon, at relevant clinical concentrations, produced dose-related inhibition of streptokinase-mediated fibrinolysis. In addition, Sulfamylon had no intrinsic fibrinolytic activity. This antifibrinolytic property of Sulfamylon solution may, in vivo, protect against early graft loss when used on burn wounds and other potentially contaminated graft sites.