Intravenous administration of radiographic contrast agents results in the occasional occurrence of thrombotic complications, which are more common after the use of ionic agents than nonionic agents. To investigate the pathophysiologic basis of this thrombotic tendency, we compared the effects of ionic and nonionic contrast agents on endothelial cells in vitro. Exposure of cultured human umbilical vein endothelial cells to ionic contrast medium for 10 minutes resulted in lifting of 76% +/- 8% of cells, significantly greater than that after exposure to nonionic medium (6% +/- 4%; p less than 0.005). A modified Baumgartner chamber was used to evaluate the effects of contrast agents on adhesion of platelets in anticoagulated whole blood to everted segments of fresh or stored deendothelialized rabbit aorta segments. Exposure of fresh vessels to ionic contrast medium led to a significant increase in platelet adhesion (31% +/- 7%; p less than .01), whereas the increase was smaller after exposure to nonionic contrast medium (25% +/- 3%). Platelet adhesion to stored vessels (41% +/- 4%) was significantly greater than adhesion to fresh aorta segments (15% +/- 2%; p less than 0.001), and contrast agents did not further increase adhesion. Microscopic examination of perfused aorta segments exposed to ionic contrast medium showed platelet adherence to intact endothelial cells, a phenomenon that did not occur without prior exposure of fresh aorta segments to ionic contrast medium. These findings demonstrate that exposure of endothelial cells to ionic contrast medium results in marked changes in cell viability and adhesive properties that may contribute to their thrombotic potential.