Myocardial structure of left ventricular segments with recurrent myocardial ischemia was evaluated by morphometry and compared with that of segments with normal blood supply in 15 patients with exercise-induced myocardial ischemia. Left ventricular high-fidelity pressure measurements and simultaneous biplane angiocardiography were performed in patients at rest and during supine bicycle exercise. Left ventricular transmural biopsy samples were obtained during open heart surgery in a normally contracting region and in a region with exercise-induced de novo wall motion abnormalities. Transmural and endocardial and epicardial left ventricular muscle fiber diameter and interstitial nonmuscular tissue were determined by morphometry. Eight patients were restudied 8 months after successful bypass grafting. Heart rate and left ventricular end-diastolic pressure increased significantly preoperatively and postoperatively during exercise. However, left ventricular end-diastolic pressure was significantly higher preoperatively (33 mm Hg) during exercise than postoperatively (19 mm Hg; p less than .01). Left ventricular ejection fraction dropped significantly during exercise (63% vs 54%; p less than .001) before surgery but remained unchanged (64% vs 66%; NS) after revascularization. Regional axis shortening of the normokinetic region increased slightly during exercise pre- and postoperatively, but decreased in the hypokinetic region from 42% at rest to 25% during exercise (p less than .001) before surgery and from 47% at rest to 41% during exercise (p less than .05) after revascularization. Transmural muscle fiber diameter (normal less than or equal to 23 microns) was significantly larger in regions with exercise-induced ischemia (29.3 microns, p less than .025) than in normally contracting regions (27.3 microns). Interstitial nonmuscular tissue (normal less than or equal to 10%) was significantly increased in regions with exercise-induced wall motion abnormalities (19.8%) compared with normally contracting regions (15.5%; p less than .05). In the endocardial half of left ventricular segments with recurrent myocardial ischemia interstitial tissue was significantly increased (23.7%; p less than .01) compared with that in the epicardial half of the same segment (17.5%). It is concluded that structural alterations of the myocardium (muscle fiber hypertrophy and increased interstitial nonmuscular tissue) develop especially in the endocardial layers of the transiently ischemic myocardium with normal function at rest.(ABSTRACT TRUNCATED AT 400 WORDS)