The acute and chronic electrocardiographic effects of diltiazem, a drug which inhibits calcium passage through slow channels, were examined both at rest and during symptom-limited exercise. In the acute study, 12 patients with coronary artery disease (CAD), three patients with hypertrophic cardiomyopathy (HCM), and one patient with both CAD and HCM performed symptom-limited upright exercise prior to and one hour after receiving 120 mg oral dose of diltiazem. In the chronic study, three dose levels of diltiazem (120 mg/day, 180 mg/day, 240 mg/day) were compared with placebo in ten patients with CAD. Each patient received one week of placebo followed by placebo or diltiazem in a double-blind random cross-over fashion, so that each patient received four weeks of placebo and three weeks of diltiazem, one week at each dose level. Each week, symptom-limited upright exercise testing was performed. In the acute study, diltiazem did not significantly affect the mean PR, QRS, QTC intervals or the heart rate at rest or at maximal exercise. In one patient, diltiazem markedly slowed the ventricular response to atrial fibrillation and in another patient, provoked transient Mobitz I block. In the chronic study, the only significant difference observed was a prolongation of the resting PR interval on the 240 mg/day dose schedule (p less than .005).