To test whether a nonionic, low-osmolality contrast medium (iopamidol) administered for coronary angiography was less harmful to renal function than ionic, high-osmolality medium (sodium diatrizoate), a prospective, double-blind randomized study of 70 patients with normal or mildly depressed renal function (serum creatinine < or = 2.0 mg/dL (175 mumol/L) was performed. Creatinine clearance was determined before coronary angiography and 24 and 48 hours after. There were no significant differences between the low- and high-osmolality groups with regard to age, baseline creatinine clearance, or dose of contrast medium given. In patients receiving low-osmolality medium (n = 35), creatinine clearance decreased by 19% +/- 13 (1 standard deviation) at 24 hours and recovered by 48 hours. In patients receiving high-osmolality medium (n = 35), creatinine clearance decreased by 40% +/- 16 at 24 hours and remained depressed by 47% +/- 14 at 48 hours. In patients with normal or mildly depressed renal function, use of a non-ionic, low-osmolality contrast medium minimized nephrotoxicity as measured by reductions in creatinine clearance after coronary angiography.