This study was conducted to characterize the alterations in serum ionized calcium induced by contrast media (CM) and to determine the cause of the change. Fresh human blood samples as well as an electrolyte solution (ES) containing 1.2 mM calcium ions were diluted with CM and alterations in ionized calcium were measured using an electrometer. The CM tested were diatrizoate, iopamidol, iohexol, ioxaglate, isotonic saline, Na2-Ca-EDTA and pure meglumine. When CM were mixed with blood, ionic CM produced a greater decrease in ionized calcium than nonionic CM or saline. When mixed with ES, a significant reduction of ionized calcium was induced by ioxaglate and diatrizoate in comparison with saline. Na2-Ca-EDTA and meglumine caused no reduction in ionized calcium. Ioxaglate and diatrizoate caused calcium binding due to anions; binding induced by the latter was more prominent than that by the former. These observations suggest that a nonionic CM is more desirable for coronary arteriography of high-risk patients.