Systemic hemodynamics and regional myocardial blood flows were determined in 18 miniswine during the development of pressure-overload hypertrophy induced by supravalvular aortic constriction. Nine miniswine served as control animals. Regional myocardial blood flows were measured at rest and during exercise stress with radioactive microspheres after 2 days and 1 month of aortic constriction. Exercise stress, causing the heart rate to increase to 85% of its maximum, was imposed twice weekly for 5 minutes on 13 pressure-overloaded animals to elicit differences between the control and experimental groups that might not occur at rest. At rest, regional myocardial blood flows of pressure-overloaded animals were similar to those of control animals. When exercise stress was imposed after 2 days and 1 month of pressure overload, endocardial blood flows decreased 45% below control exercise levels, although epicardial blood flows were unchanged. During the first 2 weeks of pressure overload epicardial and endocardial electrocardiograms showed S-T segment elevation with exercise stress but not at rest. Postmortem examinations after 1 month of pressure overload showed significant histologic evidence of myocardial injury, namely, fibrosis, which was subendocardially located. These findings indicate that the pressure-overloaded heart is at risk for ischemic injury, particularly during the early, uncompensated stage.