Background: Previous studies showed low resting phosphocreatine/adenosine triphosphate (PCr/ATP) ratios within this patient population compared with controls; however, these low PCr/ATP did not correlate with endomyocardial biopsy rejection. One possible explanation is the presence of cardiac allograft vasculopathy (CAV), which might be manifested as a transient ischemic event in the mildly stressed transplanted heart. If transient ischemia is invoked through the 31P magnetic resonance spectroscopy (MRS) stress test, monitoring of such an event should be achievable and thus implicating possible ischemic involvement. Methods: Heart transplant patients (n = 25) and normal controls (n = 11) were studied using the 31P MRS stress test; 10 patients tested positive (> 2 standard deviations [SDs] from control values). Patients also were monitored for heart rate and blood pressure with the handgrip exercise generating a small increase in the rate-pressure product. Results: The percent change (%Δ) in the PCr/ATP ratio in the control group was 1.50% ± 10.6; the transplant population showed an overall change of -6.7% ± 18.5. The responders, those that were at or below the 2 SD line from control, had a -25.6 ± 3.6% Δ PCr/ATP; whereas the non-responders reflect a 5.1 ± 13.4%. The responders' response is quite striking when considering the threshold for an abnormal PCr/ATP %Δ in response to stress testing was -19.7%, which was the 2 SD mark below the mean value for the reference population. Discussion: The 31P MRS stress test showed that a possible transient ischemic event occurred in a subset of patients, thus implicating possible CAV in the cardiac transplant patient. Such an approach may provide an early diagnosis of this disease.