The distribution of 125I iothalamate between the intravascular and extravascular fluid compartments was determined after intravenous injection in dogs. Simultaneous measurements of total blood volume, blood iothalamate concentrations and urinary iothalamate excretion were made and permitted calculation of extravascular iothalamate. The drug diffused very rapidly to the extravascular space: more than half had reached the extravascular space one minute after injection. The ratio of extravascular to intravascular iothalamate rose to a plateau of 6.8. We conclude that the contrast material responsible for tissue opacification during radiography is primarily extravascular and that the levels of contrast in plasma during urography are affected less by renal excretion than by distribution between fluid compartments.