To explore the potential role of MRI in detecting cardiac allograft rejection in transplant recipients using gadolinium tetraazacyclododecane tetraacetic acid (Gd-DOTA) for contrast enhancement, we examined 7 normal healthy volunteers and 39 patients separated into three groups according to histological findings. Quantitative myocardial enhancement (ME), expressed as the ratio of maximum signal intensity after intravenous Gd-DOTA injection to signal intensity before intravenous injection of Gd-DOTA, was significantly lower for patients without histological rejection (n = 14; regional ME = 83 +/- 41%; mean ME = 53 +/- 24%) when compared with patients with grade 1 histological rejection (n = 18; regional ME = 122 +/- 20%, p = 0.02; mean ME = 70 +/- 14%, p < 0.05) and with patients with grade 2 or 3 rejection (n = 7; regional ME = 135 +/- 44%, p = 0.02; mean ME = 81 +/- 27%, p < 0.05). Myocardial enhancement was not significantly different in patients with grade 1 histological rejection compared with patients with grade 2 or 3 rejection. Because predominant focal areas of ME were observed in all patients, regional ME seemed a better measurement than mean ME to distinguish focal histological changes when the rejection process is beginning. More sophisticated software analysis is necessary to quantify and map high ME to establish the exact relationship between the extent of edema and the severity of rejection.