To assess the effect of diltiazem on left ventricular systolic regional wall motion and diastolic function in patients with coronary artery disease (CAD), 22 patients underwent biplane left ventricular cineangiography before and after intravenous diltiazem (plasma concentration 154 +/- 12 ng/ml). Left ventricular and right ventricular pressures were measured by micromanometer-tipped catheters. Regional wall motion was assessed quantitatively with an area ejection fraction technique. Diltiazem decreased mean arterial pressure 11.5% (p less than .0001) and heart rate 6.8% (p less than .005); it increased cardiac index 8.8% (p less than .025) and global ejection fraction 9.1% (p less than .0001). However, left ventricular end-diastolic pressure increased 14.2% (p less than .001) and the left ventricular end-systolic pressure-volume (P-V) ratio decreased 8.8% (p less than .02). Diltiazem decreased the time constant of left ventricular relaxation by 14.3% (p less than .002), despite lack of change in the left ventricular diastolic P-V relationship, in 16 patients. Diltiazem caused a significant increase in area ejection fraction in 53% of hypokinetic areas supplied by diseased arteries compared with 13% of normokinetic areas supplied by diseased arteries (p less than .0001). Response of ejection fraction to diltiazem in areas supplied by normal coronary arteries was less (p less than .05) than that in hypokinetic areas supplied by arteries affected by disease. In conclusion, diltiazem improves regional wall motion abnormalities in patients with CAD and the improvement is associated with better left ventricular relaxation but not with a change in the diastolic P-V relationship. Global indexes of left ventricular systolic performance are favorably influenced by diltiazem, despite a mild negative inotropic effect.