Quantitative radionuclide angiography (with the first pass technique and a computerized multicrystal camera) was used to evaluate hemodynamic changes in three subject groups during symptom-limited upright exercise. The 12 normal subjects had significant increases in heart rate, stroke volume, left ventricular ejection fraction and cardiac output during exercise; changes in end-diastolic and end-systolic volumes were not significant. In the 24 patients with coronary artery disease there were significant increases in heart rate and cardiac output during exercise, but insignificant changes in end-diastolic, end-systolic and stroke volumes and ejection fraction. The change in diastolic volume in these patients was determined by the extent of coronary artery disease, propranolol therapy, end point of exercise and presence of collateral vessels. Furthermore, patients with previous myocardial infarction had a lower ejection fraction and higher end-diastolic and end-systolic volumes during exercise than those without myocardial infarction. In the 12 patients with chronic aortic regurgitation of moderate to severe degree, there was a decrease in the end-diastolic volume during exercise. This response was distinctly different from that of the normal subjects or the patients with coronary artery disease. All three groups had a significant decrease in pulmonary transit time during exercise. It is concluded that changes in cardiac output in normal subjects during upright exercise are related to augmentation of stroke volume and tachycardia, whereas in patients with coronary artery disease they are related mainly to tachycardia. Left ventricular dilatation during exercise occurred in some normal subjects and in patients with coronary artery disease but was not a consistent finding. However, a decrease in left ventricular end-diastolic volume is common in patients with aortic regurgitation. Such a decrease may be explained by a reduction in the regurgitant volume per beat caused by shortening of the diastolic filling period or a decrease in systemic vascular resistance, or both.