Diabetes mellitus was induced in rats with streptozotocin and after 3 months the animals (n = 48) received an i.v. injection of 1 or 3 g I/kg in the form of high-osmolar diatrizoate, low-osmolar iopromide or iohexol, or of 0.6 g I/kg of high-osmolar Gd-DTPA. The controls were given an i.v. injection of physiologic saline. After 2 hours the kidneys were fixed by perfusion and the renal morphologic changes were semiquantitatively analyzed by two independent observers unaware of the agent administered. The contrast media (CM) induced pronounced cytoplasmic vacuolization in the proximal convoluted tubular cells. Such a lysosomal alteration may indicate CM uptake into the cell, and the ultrastructural evaluation revealed intracellular injuries related to the process. The alterations were most marked following administration of iohexol, but diatrizoate also induced a statistically highly significant vacuolization (p < 0.001). The lysosomal alterations following iopromide administration were not as striking, and Gd-DTPA induced only minor changes.