The safety and efficacy of iohexol, a new nonionic contrast agent, were compared with a diatrizoate (Renografin-76) in a double-blind, parallel study of peripheral arteriography by femoral puncture in 60 patients. Extra-large field serial peripheral arteriography was used and a posterior tibial nerve block was applied to all patients in the study. Similar changes in blood chemistry were observed following the injection of iohexol and diatrizoate but these changes did not require corrective measures. Significantly more patients complained of a sensation of severe heat after receiving diatrizoate (38%) than after the injection of iohexol (10%) (p = 0.001). Four patients in the diatrizoate group experienced one or more adverse reactions, including mild urticaria. Only mild nausea was reported by a single patient in the iohexol group. Overall, 100% of the studies were diagnostic but more of the radiographs taken after the injection of iohexol were rated excellent than after the injection of diatrizoate.