Apparent cavity dilatation is a common finding during exercise tomographic thallium scintigraphy in patients with hypertrophic cardiomyopathy. To investigate the mechanism of apparent cavity dilatation, 50 patients with hypertrophic cardiomyopathy underwent exercise thallium scintigraphy, catheterization study, and radionuclide angiography. In the 26 patients with apparent cavity dilatation on thallium scintigraphy, left ventricular outflow tract gradients (61+-48 vs 27+-35 mmHg, p<0.01) and left ventricular end-diastolic pressure (20+-7 vs 16+-6 mmHg, p<0.05) were higher, and maximum provocable gradients tended to be higher (114+-35 vs 89+-54 mmHg) compared to the 24 patients without apparent cavity dilatation on thallium scintigraphy. Ejection fractions and indices of diastolic filling at rest were similar between the two groups. However, the 26 hypertrophic cardiomyopathy patients with apparent cavity dilatation on scintigraphy were more likely to have myocardial ischemia (myocardial lactate production) during pacing at 150 beats per minute (21 of 26 vs 10 of 24, p=.01), have higher left ventricular end-diastolic pressures post pacing (32+/-5 vs 24+/-10 mmHg, p<0.01) and have associated increased lung uptake of thallium with exercise (14 of 26 vs 2 of 24, p<0.002). Thus, stress induced apparent cavity dilatation may result from ischemia-related diastolic dysfunction leading to endocardial compression and elevated pulmonary pressures, and is most likely to occur in patients with high basal left ventricular outflow gradients and left ventricular end-diastolic pressures.