Silent myocardial ischemia is a frequent finding when Holter monitoring is done in patients with advanced coronary disease. Silent ischemia is associated with a worse prognosis in patients with stable or unstable angina, survivors of myocardial infarction, and populations at risk for coronary disease. Whether medical therapy for silent ischemia improves prognosis is not known. In a randomized, placebo-controlled, multicenter trial of 60 patients with documented coronary disease, positive exercise tests, and ischemic episodes on Holter monitoring, long-acting diltiazem reduced ischemic episodes by 50% compared to placebo, from a mean of 5.6 to 2.8 (p less than 0.0001). Efficacy was maintained over 24 h and diltiazem also significantly improved exercise test parameters. Three smaller studies also demonstrated that diltiazem effectively reduces ambulatory ischemia; however, results with nifedipine are conflicting, with several studies showing no benefit. In contrast, beta-blockers reliably reduce ischemic episodes. The role of medical therapy for silent ischemia will be clarified only when its effect upon morbidity and mortality are determined.