Combined nitrate/beta-blocker/nifedipine therapy is commonly used to treat refractory angina pectoris. We have observed "paradoxical" myocardial ischemia in ten patients with refractory angina (seven receiving combined beta-blocker and nitrate therapy, and three receiving nitrate treatment alone) in whom nifedipine (mean dosage, 92 mg/day; range, 60 to 120 mg/day) induced a decrease in blood pressure, angina pectoris (10/10 patients), and ischemic ECG changes (7/10 patients). These ten patients, all of whom regularly reported angina within 20 to 30 minutes of nifedipine ingestion, were prospectively studied before and after usual nifedipine dose administration, while blood pressures, heart rate, and ECGs were recorded. Mean systolic BP fell from 109 to 94 mm Hg after nifedipine (P less than .001, paired t test); mean heart rate increased from 64 to 68 beats per minute (P less than .05); seven patients developed transient ECG changes (five with ST-T wave depression and two with ST-T wave elevation) during the hypotensive period. Nifedipine may provoke angina and myocardial ischemia in certain patients with refractory angina pectoris receiving concomitant beta-blocker and nitrate therapy.