To determine the systemic and coronary hemodynamic effects of diltiazem at rest and during pacing, 14 patients with stable angina pectoris undergoing coronary angiography were studied before and after 0.165 mg/kg (n = 7) and 0.25 mg/kg (n = 7) of intravenously administered diltiazem. Hemodynamic variables, metabolic measurements and left ventricular (LV) ejection fraction (EF) were obtained at rest and during coronary sinus (CS) pacing before and during diltiazem administration. Lactate production during control pacing turned into extraction after diltiazem (p less than 0.05). At rest, systemic resistance was reduced by 21% (p greater than 0.01) and mean arterial pressure by 12% (p less than 0.01); cardiac index increased from 2.4 +/- 0.4 to 2.6 +/- 0.4 liters/min/m2 (p less than 0.01), with no significant change in heart rate. The mean pulmonary artery pressure increased from 17 +/- 2 to 19 +/- 3 mm Hg (p less than 0.01), but other hemodynamic variables were not affected. Diltiazem given during pacing reduced the mean aortic pressure (from 112 +/- 15 to 104 +/- 15 mm Hg, p less than 0.05), but other hemodynamic variables were not affected significantly. LVEF decreased 16%, from 0.63 +/- 0.9 to 0.53 +/- 0.8 with CS pacing (p less than 0.01); when the pacing was performed after diltiazem administration the 8% decrease in LVEF from 0.64 +/- 0.09 to 0.59 +/- 13 was less marked (p less than 0.01). Diltiazem had no significant effect on LVEF at rest. The overall data suggest that the ischemic manifestations of CS pacing are attenuated by diltiazem in doses of the drug that exert no significant depressant effect on LV function in patients with coronary artery disease.