To assess the relative role of increased ventricular preload and critical coronary lesions in ergonovine-induced myocardial ischemia, 9 normal subjects (group A), 7 patients with stable angina (group B) and 5 with variant angina (group C) were studied. In all patients, the 12-lead electrocardiogram, blood pressure and left ventricular (LV) volume (technetium-99m blood pool) were continuously recorded before and during administration of incremental doses of ergonovine given at 5-minute intervals. In all subjects, an initial LV dilatation developed; in group B and C patients, this was followed by a decrease in stroke volume and ejection fraction with subsequent onset of electrocardiographic changes and angina. The interval between these events was significantly shorter in group C and in 3 group B patients; in these patients, signs of ischemia appeared with smaller ergonovine doses and at minimal preload increase, coronary constriction being the likely mechanism of ischemia. In the remaining 4 group B patients, the onset of stroke volume, ejection fraction, electrocardiographic changes and angina was significantly delayed, occurring after administration of larger ergonovine doses when LV volume was already considerably increased. This finding suggests that the loading effect of ergonovine on LV volume, rather than on coronary constriction, could be the prevailing mechanism of ergonovine-induced ischemia in these patients.