The effect of radiological contrast media on blood flow through a vascular network was investigated, taking physical and physiological conditions such as osmolality into account. The perfusion of the bullfrog's hind limbs was performed, with a slight modification of the vertical tube method. The effect of contrast media on red cell deformability was studied by perfusion with erythrocyte suspensions in glutaraldehyde-fixed hind limbs. The echinocytic shape change induced by metrizamide and hypertonic iothalamate solutions caused a marked increase in resistance to flow. When the perfusion with erythrocyte suspension was performed using intact hind limbs, the pressure-flow relationship was influenced by contrast media effects on both red cell deformability and the vascular bed. Ioxaglate had less rheologic effect on the pressure-flow relationship than metrizamide or iothalamate. It could be concluded that contrast media should be isotonic, of low viscosity and chemotoxicity, and that ioxaglate was preferable to metrizamide and iothalamate at equal iodine content.