Diazepam (DZP) is commonly used in treatment of patients with acute ischemic syndromes to allay anxiety, but benzodiazepines reduce myocardial contractility and increase myocardial blood flow. To investigate the antiischemic effect of DZP, we studied 13 patients with a positive exercise test and angiographically documented coronary artery disease. All patients were submitted to a randomized, placebo-controlled trial using 0.9% NaCl infusion as placebo and intravenous (i.v.) diazepam (0.1 mg/kg in 20 min). Exercise tests performed immediately after the infusions showed that as compared with placebo, DZP significantly prolonged time to 1-mm ST-segment depression (557 +/- 198 vs. 428 +/- 226 s, p < 0.0001) and total exercise duration (624 +/- 177 vs. 561 +/- 188 s, p < 0.007). Rate-pressure product (RPP) at 1-mm ST-segment depression was not significantly different with the two treatments. DZP significantly delays onset of exercise-induced myocardial ischemia in patients with coronary artery disease. Because RPP at onset of ischemia was similar to that recorded with placebo despite greater levels of external workload, the antiischemic action of DZP appears to be mediated, at least partially, by a reduction in myocardial oxygen consumption.