OBJECTIVE This single-center, prospective, randomized, double-blind phase IV study in parallel-group design was carried out to investigate whether either of two different x-ray contrast media (iomeprol 350 or iopentol 350) injected into the axillary artery has any influence on cutaneous microcirculation. RESULTS The investigation was carried out on two groups of patients (n = 10 in each group) who had to undergo a diagnostic heart catheter angiography. The confirmatory response variable for the study was the mean capillary erythrocyte velocity (mm/sec). Blood flow through the ipsilateral nail-fold capillaries was recorded continuously for 3 minutes before and 6 minutes after the injection of the randomly assigned x-ray contrast medium, and was evaluated off-line. A contrast medium-induced, rheologically determined disturbance of the microcirculation was found, which was due to two different effects. First, the high intrinsic viscosity (iopentol = 12.3 mPa.sec) led to an immediate reduction in capillary blood flow. This did not occur in the case of iomeprol (intrinsic viscosity = 7.5 mPa.sec). Second, the contrast medium molecules cause a morphological change in the erythrocyte membrane; echinocytes are formed and are further desiccated depending on osmolality of the contrast medium. CONCLUSIONS The time course of the conversion of erythrocytes into echinocytes leads to a maximum reduction in capillary erythrocyte velocity of 30 seconds after the bolus of contrast medium. For the more viscous contrast medium of higher osmolarity (iopentol), this led to a significant overall reduction of up to 48.6% in capillary blood flow (p < 0.0001) that lasted for up to 150 seconds, while iomeprol did not significantly affect capillary blood flow (p = 0.2759).