Two cases of catastrophic thrombus formation during coronary angioplasty occurred shortly after the operators began using nonionic contrast. This occurred despite systemic heparinization, the adequacy of which was documented by activated clotting times (ACT). Both cases were resistant to balloon inflation and one was refractory to intracoronary thrombolysis. There is a considerable body of evidence documenting that low-osmolality contrast media, especially those that are nonionic, have less anticoagulant effect than standard contrast media. Several reports have also been published suggesting possible relationships between nonionic contrast and intravascular thrombus formation during coronary angiography and angioplasty. These data are reviewed and recommendations made for utilization of these contrast media.