To assess whether left ventricular myocardial metabolism is affected by the presence of right ventricular pressure overload, we performed 123I-beta-methyl-iodophenyl pentadecanoic acid (123I-BMIPP) and 99Tc(m)-sestamibi (99Tc(m)-MIBI) single photon emission tomography in 24 patients with pulmonary hypertension and in 10 control subjects. The left ventricle was divided into six regions using a short-axis tomogram at the mid-ventricular level. The relative regional uptake (RRU, %) was determined for each region as the ratio of the regional uptake per pixel to the maximum uptake in the six regions. Right heart catheterization was performed to obtain mean pulmonary arterial pressure. 123I-BMIPP uptake in the septum and the adjacent myocardium of the left ventricle was lower in patients with pulmonary hypertension than in control subjects (septal RRU, 75 +/- 6 vs 85 +/- 4%; anteroseptal RRU, 76 +/- 6 vs 86 +/- 3%; posteroseptal RRU, 75 +/- 4 vs 84 +/- 4%; P < 0.001). The reduction in 99Tc(m)-MIBI uptake was confined to the septum in patients with pulmonary hypertension (79 +/- 5 vs 85 +/- 5%; P < 0.05). Interestingly, the septal RRU of 123I-BMIPP and the sum of the septal, anteroseptal and posteroseptal RRUs of 123I-BMIPP were negatively correlated with mean pulmonary arterial pressure (r = -0.70 and -0.55, respectively; P < 0.01). In conclusion, myocardial metabolism in the interventricular septum and the adjacent regions of the left ventricle may be impaired in proportion to the degree of pulmonary hypertension.