Abnormal phosphate metabolism of the myocardium was evaluated in patients with hypertrophic cardiomyopathy (HCM) using 31P magnetic resonance (MR) spectroscopy. The results were compared with those from left ventricular function and thallium 201 (Tl-201) perfusion scintigraphy. Six normal volunteers and 19 patients with HCM were studied with a 1.5 T MR system. The spectra were localized to the myocardium using volume selection with the depth-resolved surface coil spectroscopy (DRESS) technique. Peak areas of 2,3-diphosphoglycerate (DPG), phosphodiesters (PDE), phosphocreatine (PCr), and beta-ATP were determined by fitting Gaussian functions to the phased spectra. The peak areas were corrected for contamination of blood adenosine triphosphate (ATP) and PDE. The corrected PCr/beta-ATP ratio in patients (1.07 +/- 0.10, mean +/- SE) was significantly lower compared with that in normal volunteers (1.71 +/- 0.13, p < .01). The PCr/beta-ATP ratio showed an abnormal decrease (< mean -2 SD of the controls) in 11 (58%) of 19 patients. The averaged PCr/beta-ATP ratio in 15 patients with normal left ventricular ejection fraction (LVEF) was 1.14 +/- 0.10, significantly lower than in healthy subjects. By contrast, the corrected PDE/PCr ratio in HCM did not differ significantly compared with that in healthy subjects (0.46 +/- 0.09 vs 0.36 +/- 0.09). The PDE/PCr ratio was abnormally elevated (> mean + 2 SD of the controls) in only four (21%) of the patients. On Tl-201 myocardial single-photon emission computed tomography (SPECT) imaging, the perfusion of the left ventricular wall looked normal in 6 and abnormal in 5 of 11 HCM patients.(ABSTRACT TRUNCATED AT 250 WORDS)