Although there have been reports of clot formation in angiographic syringes containing nonionic contrast agents, these clots are now believed to be aggregates of red cells that form in the low ionic strength, low pH, zero shear rate environment of contrast media syringes. In an in vitro controlled flow system that stimulates blood flow through a microvessel, we found that large (100 microns or more) red cell aggregates are not seen with any of the media tested (iohexol, sodium methylglucamine diatrizoate, and ioxaglate); aggregates that form under shear conditions are rouleaux. The degree of rouleau formation, compared with saline controls, is greatest with ioxaglate, least with diatrizoate, and intermediate with iohexol. Platelet adhesion/aggregation at a site of injury to vascular endothelium is not significantly affected by iohexol. Rouleaux formation, a potential determinant of local levels of thrombin and other platelet-activating substances, is shown to occur in the lee of mural platelet thrombi.