Reversible thallium-201 (201Tl) abnormalities during exercise stress have been used as markers of myocardial ischemia in hypertrophic cardiomyopathy (HCM) and are most likely to identify relatively underperfused myocardium. Although metabolic abnormalities in HCM were reported, the relationship between impaired energy metabolism and exercise-induced ischemia has not been fully elucidated as yet. To assess the relationship between myocardial perfusion abnormalities and fatty acid metabolic abnormalities, 28 patients with HCM underwent exercise 201Tl and rest 123I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) scintigraphy. Perfusion abnormalities were observed by exercise 201Tl in 19/28 patients with HCM. 123I-BMIPP uptake was decreased compared with delayed 201Tl in 106/364 (29%) of the total myocardial segments (p<0.01, McNemar symmetry test). Such disparity between 123I-BMIPP and 201Tl was observed more often in the 49/75 (65%) segments with reversible exercise 201Tl defects (p<0.001). Our results indicate that exercise-induced myocardial ischemia exists in HCM, resulting in metabolic abnormalities. The combination of 123I BMIPP and 201Tl suggests that myocardial ischemia may play an important role in metabolic abnormalities in HCM.