Elevation in left ventricular (LV) end-diastolic pressure (EDP) after contrast ventriculography (CV) has been proposed as a form of stress intervention in patients with coronary artery disease (CAD). The mechanism of this change has not been delineated. Accordingly, we performed two studies in CAD patients. In study 1 (n = 10), CV was repeated 3 minutes after an initial study. LVEDP rose from 14.9 +/- 6.6 mm Hg prior to the first ventriculogram to 26.9 +/- 10.8 mm Hg 3 minutes after the first ventriculogram (p less than 0.05) and immediately prior to the repeat CV (performed to evaluate the changes in volume produced by the first ventriculogram). In four patients with LV micromanometer pressures, the entire diastolic pressure-volume relation was shifted upward. LV ejection fraction (EF) and end-diastolic volume (EDV), peak LV pressure, and peripheral vascular resistance were unchanged at the time of repeat CV, and there was no correlation between the change in EDP and any of these variables. In study 2 (n = 6), gated radionuclide angiography was performed prior to and at minutes 2 to 7 after CV as were measurements of LV and right ventricular (RV) pressures. While both LV and RV EDP rose following contrast ventriculography, LV and RV EDV and EF were unchanged. We conclude that alterations in LVEDP after CV are unrelated to changes in LV or RV EDV and are most likely mediated by a decrease in myocardial compliance.