Fatty acid metabolic and perfusion abnormalities associated with cardiac hypertrophy were investigated using dual tracer tomography with thallium and a cardiac metabolic tracer, 15-(p-iodophenyl)-3-R, S-methylpentadecanoic acid (BMIPP), in eight patients with hypertrophic cardiomyopathy (HCM) and in three with hypertension (HT). Thallium and BMIPP uptakes were scored and analyzed in 143 segments (13/heart) by comparison with the left ventricular wall thickness measured by two-dimensional echocardiography. Complete agreement of both scores in HT patients was significantly higher than that in HCM patients (64% vs 24%, p < 0.001), while a lower BMIPP uptake compared to that of thallium (mismatching) was observed more frequently in HCM than in HT patients (65% vs 31%, p < 0.001). The wall thickness significantly (p < 0.005) correlated with BMIPP uptake score. HCM patients showed a low BMIPP uptake in 22 hypertrophic segments (59%) and 15 non-hypertrophic segments (41%), and reduced BMIPP uptake in 29% hypertrophic segments, while HT patients showed just five segments with decreased BMIPP uptake of which 4 were non-hypertrophic and only one hypertrophic. The left ventricular ejection fraction assessed by radionuclide ventriculography was normal and no regional wall motion abnormality was detected in any patient by echocardiographic and scintigraphic studies. Metabolic abnormalities detected by the iodine-123-beta-methyl fatty acid analog in hypertrophic cardiomyopathy may be independent of thallium myocardial perfusion, regional wall motion, or the magnitude of cardiac hypertrophy, suggesting that fatty acid imaging may be useful in investigating the pathogenesis and subclinical abnormality of hypertrophic cardiomyopathy, and differentiation from secondary, induced cardiac hypertrophy.