Global and regional systolic function during exercise were studied at cardiac catheterization with biplane cineangiography and micromanometer pressures in three groups of patients: an ischemia group (n = 22) with exercise-induced asynergy from coronary artery disease, a control group with no or minimal cardiovascular disease (n = 5) and a "scar" group (n = 5) with prior infarction and no new asynergy with exercise. Ventricular emptying curves at rest did not distinguish patients with coronary artery disease from control subjects. During exercise, end-systolic volume increased in all patients in the ischemia group; ejection fraction decreased from 62 to 51% p less than 0.001) despite an increased end-diastolic volume. Stroke volume decreased from 65 to 58 ml/m2 (p less than 0.001) and limited the average increase in cardiac index to 65%. The scar group had no decrease in stroke volume, but end-systolic volume failed to decrease during exercise, as it did in all control subjects (35 to 28 ml/m2, p less than 0.05). An exercise-induced decrease in peak left ventricular pressure in five patients (23%) in the ischemia group was not accompanied by more severe or extensive ischemia as judged by ejection phase indexes. There was a tendency for maximal positive first derivative of left ventricular pressure (dP/dt) to be less (1,912 versus 2,446 mm Hg/s, difference not significant), suggesting an abnormality of pressure generation, not shortening. Global function during exercise in the ischemia group was determined, in part, by the extent of regional dysfunction. Those in whom between three and five regions of eight regions studied had abnormal fractional shortening during exercise had a 6% decrease in ejection fraction, while those with six to eight abnormal regions had a decrease in ejection fraction of 15% (p less than 0.05). In addition, function of nonischemic, noninfarcted myocardium was studied at the base of the left ventricle in those with exercise-induced anteroapical ischemia (n = 4) and those with anteroapical infarction (n = 4). Base fractional shortening and shortening velocity were greater at rest in those with infarction (39% and 1.6 circ/s, respectively) than in control subjects (31% and 1.0 circ/s, respectively, p less than 0.01), indicating a chronic augmentation of shortening. Base shortening velocity during exercise in those developing anteroapical ischemia increased from 1.1 to 1.4 circ/s (p less than 0.005), suggesting an acute augmentation of function balancing the deterioration of anteroapical function. Systolic function in coronary artery disease is determined by acute and chronic alterations in regional function. During exercise, there is an interplay between regional dysfunction from ischemia or infarction and regional hyperfunction of nonischemic myocardium which determines global performance.