The authors report the first clinical experience in the United States with the highly water soluble, nonionic dimer (6:1 ratio) contrast medium iodixanol (5,5'-[(2-hydroxyl-1,3-propanediyl) bis(acetylimino)] bis[N,N'-bis(2,3dihydroxypropyl)-2,4,6-triodo1,3-benzenedicarbooxamide]). Iodixanol has an osmolality less than half that of monomeric, nonionic equivalent contrast media. Sodium, calcium, and magnesium ions were added to iodixanol to make the injected solution isosmotic to blood (290 mosm/kg H2O), With levels of free calcium and magnesium equivalent to levels found in the blood. Forty patients undergoing elective excretory urography were studied after bolus injection of doses of iodixanol with either 27 or 32 g of iodine. No adverse event or idiosyncratic reaction occurred. Seven patients felt coolness at the site of injection. Diagnostically adequate urographic examinations were routinely obtained with both doses. Further clinical investigation with iodixanol is warranted to determine if its beneficial chemical properties minimize both the chemotoxic and osmotoxic side effects and the disruption of physiologic functions that are seen with use of other ionic and nonionic contrast media.