The effects upon the rabbit blood-brain barrier after intracarotid injection of two non-ionic contrast media, iopentol (a monomer) and iodixanol (a dimer) were compared. Iothalamate and iohexol were used as reference substances. 99Tcm-DTPA, 125I-HSA and Trypsin blue were used as tracers in order to demonstrate various degrees of damage to the barrier. Injection of iothalamate led to large extravasation of 99Tcm-DTPA, 125I-HSA and Trypan blue which means severe damage of the blood-brain barrier. Injection of iopentol and iohexol resulted in some extravasation of all three tracers used, whereas injection of iodixanol only led to extravasation of the small molecule tracer 99Tcm-DTPA demonstrating minor changes of the barrier. At computed tomography of the brain with intravascular contrast medium enhancement it is safer to use iodixanol than iothalamate. Iodixanol is expected to cause even less adverse effects to the brain after intraarterial injection than iopentol and iohexol.