Some patients with hypertrophic cardiomyopathy (HCM) demonstrate abnormal myocardial long-chain fatty acid (LCFA) metabolism. However, the exact mechanism involved is unknown. Recently, it was proposed that myocardial cells take up LCFAs via a specific mechanism, in which the CD36 molecule has been implicated as a possible candidate molecule. In addition, a high prevalence of CD36 deficiency was also found in a small number of HCM patients. Accordingly, the investigation of abnormality of the CD36 molecule in a large number of HCM patients may be useful in finding the possible cause of HCM. Moreover, the analysis of myocardial LCFA uptake in patients with molecular abnormalities may be helpful in understanding the possible function of this molecule. In this study, in order to discover the relationship between HCM and the CD36 molecular abnormality, the expression level of platelet CD36 and CD36 cDNA in 55 HCM patients was analyzed. Twelve patients showed negligible (<5%) CD36 expression on their platelets. Among them, one was found to be homozygous for the C-478-->T substitution and 6 were heterozygous for the C-478-->T substitution. In 9 patients, CD36 was expressed by less than 50% of the platelets. One of them was found to be heterozygous for the C-478-->T substitution. Two other patients were also found to be heterozygous for this point mutation, although their platelets expressed CD36. Thus, 23 out of 55 (41.8%) HCM patients had negligible (<5%) or reduced (<50%) levels of CD36 expression on platelets, or had a point mutation of CD36 cDNA. These 55 HCM patients were also evaluated with myocardial scintigraphy both for LCFA uptake and perfusion, which showed a moderate to severe discrepancy between myocardial LCFA accumulation and myocardial perfusion in 95.5% of the patients (21/23). On the other hand, 70% of the patients with normal (>90%) CD36 expression (14/20) did not show any severe discrepancies between myocardial LCFA accumulation and myocardial perfusion. These data could suggest that abnormal myocardial LCFA metabolism seen in HCM patients may be related to abnormality of the CD36 molecule, and that abnormalities of this molecule may be linked to the cause of some types of HCM.