OBJECTIVE To evaluate the platelet activation and aggregation produced by ionic high-osmolality contrast media (HOCM) and both ionic and nonionic low-osmolality contrast media (LOCM). METHODS After each agent was mixed with heparinized blood, sequential platelet counts were used to monitor platelet aggregation, and flow cytometry was used to monitor both aggregation and activation. Aggregation was measured with CD41a-FITC (specific for glycoprotein IIb-IIIa) and activation was measured with CD62-PE (specific for P-selectin). RESULTS High concentrations of the nonionic LOCM (> 31% by volume in whole blood) induced more than 90% platelet activation within 2 minutes of exposure to freshly drawn heparinized whole blood. Aggregation followed immediately after activation and was somewhat reversible. High concentrations of the ionic HOCM (> 31%) induced prominent activation, although it occurred at a much slower rate and to a lesser degree than with the nonionic media. There was approximately 70% activation after 45 minutes of exposure. Ionic HOCM inhibited platelet aggregation, however. The ionic LOCM ioxaglate produced minimal or no platelet aggregation or activation. CONCLUSIONS There is likely to be an agent-related difference in the risk of platelet activation and aggregation in the catheter lumen and in the immediate environment of the catheter tip, where high concentrations of contrast media are known to exist.