Previous observations and clinical manifestations suggest the presence of ischemia in the disproportionately thickened septum of patients with hypertrophic cardiomyopathy. Metabolic consequences of ischemia can be demonstrated with positron emission tomography. Therefore, 10 patients with hypertrophic cardiomyopathy and an echocardiographic septum to posterior wall thickness ratio of 1.8 +/- 0.4 cm (range 1.3 to 2.5) were studied with the use of nitrogen (N)-13 ammonia, carbon (C)-11 palmitate and fluoro (F)-18 2-deoxyglucose as tracers of myocardial blood flow, fatty acid metabolism and exogenous glucose utilization. The results of positron emission tomography in 9 patients with hypertrophic cardiomyopathy were compared with those in 10 normal volunteers. In the hypertrophic cardiomyopathy group, observed myocardial activity of N-13 ammonia and C-11 palmitate in the septum was similar to that in the lateral wall. Septum to lateral wall tissue activity ratios averaged 1.04 +/- 0.15 for N-13 ammonia and 1.04 +/- 0.18 for C-11 palmitate, and were similar to those in the normal volunteers (0.98 +/- 0.07 and 0.98 +/- 0.03, respectively; p = NS). Myocardial clearance half-time and residual fraction of C-11 palmitate did not differ significantly between the septum and lateral wall. However, F-18 2-deoxyglucose uptake was significantly lower in the septum than in the lateral wall (15,768 +/- 4,314 versus 19,818 +/- 5,234 counts/pixel; p less than 0.003). The mean septum to lateral wall activity ratio of 0.83 +/- 0.21 was less than that observed in normal volunteers (0.92 +/- 0.07; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)