The changes in density of specific tissues after administration of intravenous contrast agents is easily detectable by computed tomography and is important in distinguishing normal and pathologic tissues. The time course of these density changes was determined in nine specific tissues in the rat by measuring tissue radioactivity after intravenous administration of 125I iothalamate. The effect of dose variations and the distribution of contrast between the extravascular and intravascular spaces in each tissue were studied as well. Most tissues showed a peak in contrast concentration immediately after injection and displayed a steady fall in concentration thereafter. In most tissues, the concentration was directly proportional to the administered dose. In liver and kidney, however, there was a relative delay in peak concentrations; concentrations were not directly proportional to the two administered doses and presumably reflected active accumulation. In all tissues, most of the contrast material was in the extravascular rather than the intravascular space within 1 min after administration; the ratio of contrast in the extravascular space to the total amount of contrast in each tissue rose steadily thereafter. These observations reveal significant differences among tissues in the distribution of contrast agents, which should be useful in the planning of CT protocols.