We compared the damage resulting from intradermal injection of four commonly used radiographic contrast media in laboratory rats. Sixty percent meglumine diatrizoate (Reno M 60) and ioxaglate (Hexabrix) produced significantly more ulceration and crusting on gross inspection and more necrosis, edema, and hemorrhage on histologic evaluation than iopamidol 300 (Isovue) or 0.9% (normal) saline. Thirty percent meglumine diatrizoate (Reno M Dip) had an intermediate toxicity, resulting in significantly more visible swelling and more microscopically detected hemorrhage than iopamidol or saline, but less ulceration/crusting and necrosis than Reno M 60 and ioxaglate. Since the three contrast agents of similar osmolality produced different degrees of tissue damage, our results suggest that factors other than high osmolality are partially responsible for determining the severity of injuries from extravasated contrast media.