The purpose of this study was to evaluate the potential of magnetic resonance imaging (MRI) in vivo for the characterization of tissue changes associated with acute myocardial rejection after cardiac transplantation. Of 15 dogs that underwent heterotopic cardiac transplantation, six served as untreated controls, and nine received immunosuppressive therapy (25 mg/kg/day cyclosporine, 1 mg/kg/day prednisone). Serial electrocardiographically gated MRI (spin-echo technique) and histologic examinations of allograft biopsy samples were performed for each dog at 2 to 3, 7 to 10, 14 to 17, and 26 to 29 days after transplantation and immediately after animals were killed. Untreated allografts showed a significant increase (p less than .01) in T2 (spin-spin) relaxation time (T2 = 66 +/- 8 msec) and intensity values compared with values in the native hearts (T2 = 44 +/- 6 msec) as early as 1 week after transplantation. The significant difference in T2 values could be observed in vivo as well as on postmortem examination and corresponded to histologic progression of the rejection process. There was no significant difference in T1, T2, or intensity values in cyclosporine-treated allografts and native hearts except in two dogs in which T2 relaxation times and signal intensity in the transplanted hearts increased simultaneously with histologic evidence of rejection, indicating failure of immunosuppressive therapy. There was a significant correlation between histologic grading of severity of rejection and T2 relaxation times of the cardiac transplants (r = .72). Likewise, there was a significant linear relationship between T2 values in vivo and percent water content when the differences between native hearts and allografts were compared (r = .92, p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)