The long-term histologic effects of the use of two cold cardioplegic solutions (St. Thomas' and saline) were studied and compared in a model of heterotopic cardiac transplantation in rats of isogeneic strain. After cold cardioplegic arrest, hearts were stored for varying times ('minimal,' 30, or 90 minutes) in one of the solution prior to transplantation, giving a total of six groups (five animals in each group). Early assessment of myocardial injury 48 hours after transplantation was by the uptake of technetium 99m pyrophosphate and by measurement of serum creatine kinase activity. Late assessment of myocardial injury at 3 months after transplantation was by quantitative histologic examination. The findings indicated that significant myocardial fibrosis occurred in hearts stored in both solutions for the longest storage period (90 minutes) and that St. Thomas' cardioplegic formula conferred better myocadrial protection after 90 minutes' storage than did cold saline, as judged by the degree of histologic injury at 3 months (p < 0.025). Significant correlation was found between long-term histologic changes at 3 months and the uptake of technetium 99m pyrophosphate (p < 0.001) and serum creatine kinase activity (p < 0.05) assessed at 48 hours. Uptake of technetium 99m pyrophosphate and increased serum creatine kinase activity was demonstrated 48 hours after injury in animals having no detectable histologic injury at 3 months. These observations indicate that there may be technetium 99m pyrophosphate uptake and enzyme release from reversibly damaged myocardial cells.