The Shwartzman reaction is an animal model displaying histopathological vasculitis phenomena. Extravasation and swelling due to increased vascular permeability and cellular infiltration, which are hallmarks of the Shwartzman reaction, were evaluated as leakage of i.v.-injected Evans Blue dye and by histological and immunohistological characteristics in rabbits and mice. (+/-)-Thalidomide, (-)-thalidomide, (+)-thalidomide and dexamethasone inhibited the increase of vascular permeability in the local Shwartzman reaction. Histologically, the intensity of the Shwartzman reaction was reduced. In mice thrombus formation and leukocytoclastic vasculitis was inhibited by (+/-)-thalidomide and (+)-thalidomide. ICAM-1 expression was markedly reduced after (+)-thalidomide injection. Thalidomide and dexamethasone pretreatment reduced Mac-1 expression on perivascular infiltrated granulocytes. The inhibitory effect of thalidomide on vasculitis of the Shwartzman reaction may thus be related to reduction of adhesion molecule expression.