The endothelo-protective activity of a series of low-molecular oxygen-derived free radical scavengers (OFRS) was tested in rats. A model of endothelaemia provoked by intravenous administration of hydrogen peroxide was used. With each OFRS the activity in the hydrogen peroxide model was compared with that in the less specific model using the provocation by citrate as a calcium chelating agent. Relatively unspecific but biologically important OFRS, ascorbic acid, tocopherol, troxerutin and glutathione were tested in the first phase of the study. A marked optimum of endothelo-protective activity was shown with all agents, the optimum against hydrogen peroxide having been observed at doses from 3 to 50 times lower than against citrate. Ascorbic acid, troxerutin and the combination of both were also tested in another model based on leg ischaemia produced by ligature of the common femoral artery. Without OFRS, a marked increase of endothelaemia was observed after 30-60 min ischaemia showing a second peak after the release of the ligature. This second peak was completely abolished by the preventive administration of OFRS in a dose which was also effective in the hydrogen peroxide model.