The renal morphologic changes induced by intravenously injected contrast media (CMs) were studied in 40 Wistar rats which had been deprived of water 24 h before the CM injection. In the first part of the investigation, the kidneys were fixed by perfusion for light and electron microscopy 2 h after injection of 3 g iodine/kg of iopamidol, iobitridol or iohexol. Control animals received physiologic saline. In the second part of the study, the fixation was performed 48 h after the injection of the corresponding dose of iobitridol or iohexol. The structural changes were semiquantitatively evaluated by two independent observers unaware of the agent injected. The lysosomes of the proximal convoluted tubular cells showed moderate changes 2 h after the iopamidol injection. Iobitridol and iohexol induced prominent lysosomal alterations with signs of cytoplasmic injury. After 48 h, the changes induced by iobitridol had almost disappeared, whereas the iohexol group still showed a statistically significant vacuolization. Although the general physicochemical properties of iobitridol and iohexol appear similar in vitro, the different lysosomal alteration might reflect differences in their characteristics in vivo.