To determine the changes in myocardial water during acute cardiac rejection and the effects of Ciclosporin (CYA) on the myocardial water, 90 heterotopic cardiac transplants were performed in rats which were divided into 3 groups, namely those receiving 1) Lewis × Lewis isografts, 2) Lewis × Brown Norway allografts and 3) CYA treated allografts (15 mg/kg/day). The water content was measured in both recipient and donor hearts at 2, 4, 6, and 8 days after transplant. Pathological specimens were examined by light and electron microscopy, and scored on a 0 to 4+ scale of increasing evidence of rejection. The water content of the isografts showed no significant change throughout the post operative period. In contrast, the allografts had significant increase of water content as early as 2 days after transplant, compared to the isografts and recipients hearts. A significant difference in cellular infiltration was noted between isograft and allograft 4 days after transplant. CYA suppressed significantly the increase of myocardial water and cellular infiltration in the allografts. These data suggest that myocardial edema may precede cellular infiltration during the rejection process and it may be suppressed with CYA treatment. The measurement of myocardial water may be useful in early detection of acute cardiac allograft rejection and for examining the therapeutic effects of CYA.