The antithrombotic activity of a fucosylated, chondroitin-sulphate-like polysaccharide extracted from the body wall of sea cucumber, and of chemically modified derivatives of the same polysaccharide, have been assessed using a stasis thrombosis model in rabbits. Intravenous administration of the native polysaccharide reduced thrombosis in a dose-dependent manner and, at a dose of 1.5 mg/kg (60 IU/kg) body weight, completely prevented thrombosis after 10 min stasis. Removal of the sulphated fucose branches of the polysaccharide abolished antithrombotic effectiveness. After intravenous injection of an antithrombotic dose of radioactively labelled polysaccharide, a correlation was observed between removal of radioactivity from the plasma and decrease in ex vivo APTT values, demonstrating that antithrombotic effectiveness depends on the level of circulating polysaccharide rather than on an indirect effect of the polysaccharide on the vascular endothelium. Reduction of the glucuronic acid carboxyl groups in the polysaccharide did not affect its in vitro and in vivo activities. Both partial defucosylation and desulphation of the polysaccharide abolished all its anticoagulant or antithrombotic action.