Background The metabolic changes of myocardial ischemia in patients with coronary artery disease assessed by Phosphorus-31 magnetic resonance spectroscopy (MRS) have been reported previously. A significant decrease in the ratio of phosphocreatine (PCr) to ATP during handgrip exercise in a group of patients with severe coronary artery disease has been demonstrated. However, there are no reports at present that directly compare cardiac Phosphorus-31 MRS data with exercise Thallium-201 myocardial scintigraphy, now established as one of the most important clinical methods to assess myocardial ischemia. The purpose of this study was to investigate whether Phosphorus-31 MRS with handgrip exercise testing is able to detect myocardial ischemia, demonstrated by exercise Thallium-201 scintigraphy.RD(-), 1.24+-0.30; P<.05). The PCr/ATP ratio decreased significantly from 1.60+-0.19 at rest to 0.96+-0.28 during exercise (P<.001) in the RD(+) group (n=15). However, in the RD(-) group (n=12), the ratio did not change significantly during handgrip exercise (1.24+-0.30 at rest versus 1.19+-0.28 during exercise). Similarly, the ratio did not change in the control group (n=11) (1.85+-0.28 at rest versus 1.90+-0.23 during exercise).Conclusions Contrary to normal subjects or patients with fixed thallium defects, the PCr/ATP ratio was significantly altered by exercise in patients with reversible thallium defects. These results suggest that Phosphorus-31 MRS with handgrip exercise testing is a sensitive method for detecting myocardial ischemia. (Circulation. 1994;89:1709-1716.)