The effect of contrast media (CM) dilution on contrast enhancement was studied using CM representing four structurally different molecular types at osmolalities ranging from 135 to 1340 mosm/kg. Diatrizoate (ionic monomer), iopamidol (nonionic monomer), ioxaglate (ionic dimer), and iodecol (nonionic dimer) were each given at a dose of 500 mgI/kg and at concentrations of both 300 and 150 mgI/mL. Contrast media concentrations were measured using iodine 125I. Tissue blood volumes were determined using human serum albumin labeled with 131I. For each of the four CM at each of the two concentrations and after each of five time intervals following injection (0, 15, 40, 120, and 300 seconds), five rats were killed (total = 200 rats). Blood and 14 other tissues were studied. Dilution of the CM did not lead to any lower iodine tissue concentrations, iodine distribution volumes, plasma volumes, or hematocrit. The authors conclude that lowering CM osmolality by dilution with water should improve tolerance without affecting CT contrast enhancement.