Systolic and diastolic myocardial performance characteristics are altered during allograft rejection. Noninvasive diagnostic markers of allograft rejection have thus far not been found to be clinically useful and have not replaced routine endomyocardial biopsy as a method to detect rejection. We examined the clinical utility of the Index of Myocardial Performance (IMP), or the Tei index, a combined index of systolic and diastolic performance (derived as a composite ratio of isovolumetric contraction time and isovolumetric relaxation time to the ejection time), in evaluating and following cardiac allograft rejection. Twenty heart transplant recipients with moderate cellular rejection (International Society for Heart and Lung Transplantation [ISHLT] grade 3A) underwent echocardiographic assessment to derive the IMP at baseline (rejection free), during treatment of rejection, and after recovery from rejection (group I). A parallel group of 20 nonrejecters (ISHLT grade 1A) were also similarly examined to serve as controls (group II). In group I patients, there was a mean increase of IMP by 98% (p <0.0001) during the rejection episode compared with baseline. After treatment, IMP decreased to its baseline value. In the control group there was no significant change in IMP over time. An IMP increase of >/=20% from baseline had 90% sensitivity and 90% specificity in detecting high-grade cardiac allograft rejection. The change in IMP in patients with grade 3A cellular rejection was independent of both the ejection fraction at baseline and change in ejection fraction during the rejection episode. These results indicate that changes in IMP, a sensitive marker of early diastolic and systolic performance, accurately evaluate the development of, and recovery from, cardiac allograft rejection. IMP can provide a clinically useful noninvasive indicator to assess the impact of therapy for amelioration of allograft rejection.