Intravascular radiographic contrast media used in angiography, particularly nonionic contrast media, may cause activation of platelets. This study was designed to determine which properties of nonionic contrast media were potentially responsible for this action. Platelet aggregation after adenosine diphosphate stimulation was studied in the platelet rich plasma obtained from 37 patients who underwent left ventriculography using the highly sensitive method of particle counting with laser-light scattering. Platelet activation by contrast media was studied in the platelet rich plasma from healthy volunteers using flow cytometric analysis to detect platelet degranulation as P-selectin expression. There was a significant decrease in platelet aggregation in patients injected with ioxilan or iomeprol compared with patients injected with iohexol. There was a significant increase in P-selectin expression with the three groups of contrast media compared to control. The platelet activation with ioxilan or iomeprol was significantly less compared to the activation with iohexol. The comparison showed that previous generalization regarding platelet activation by nonionic contrast media might not be valid. It is presumed that the higher osmolality of iohexol may contribute to the increase in platelet aggregation and activation.