Coronary artery spasm is a known complication of coronary interventions, for which intracoronary nitroglycerin (ICN) is the treatment of choice. Some forms of intense spasm are resistant to ICN. Calcium channel antagonists are also known to be effective for coronary artery spasm, including nitroglycerin-resistant spasm. Here we describe a protocol for the clinical use of intracoronary diltiazem (ICD). By this protocol, ICD can be safely given without disturbing the clinical status of patients. ICD (2.5 mg) given slowly over 1 minute produced no vasodilitation of normal vessel segments but did produce significant dilatation of stenotic segments above and beyond the effects of nitrates. Mean minimum lumen diameter increased 18%, from 0.89 +/- 0.06 mm to 1.06 +/- 0.07 mm (mean +/- SEM, P < 0.001). ICD produced clinically insignificant changes in systolic blood pressure, diastolic blood pressure, heart rate, and PR, QRS, and QT intervals. This protocol has been employed to safely use ICD to relieve both nitroglycerin-resistant epicardial artery spasm and nitroglycerin-resistant distal microvascular spasm (the no-reflow phenomenon).