Organ pretreatment prior to transplantation has assumed increasing importance. We studied the ability to preserve and perfuse hearts in well-defined genetic mouse models, prior to heterotopic engraftment. Hearts were manually perfused through the aortic root and stored in a variety of cold solutions or were perfused using a continuous perfusion pump. Different electrolyte solutions, mouse strains, perfusion, and storage times as well as perfusion volumes were studied. Treated hearts were than transplanted heterotopically and short- and long-term function assessed. Hearts stored for more than 1 hour in cold solutions (saline 0.9%, or lactated Ringer's) failed to function. Hearts perfused with 0.25-0.4 ml of cold solution for a maximum of 30 minutes functioned well after transplantation. C3H (H-2k) mice provided the most resilient hearts. We conclude that short-term perfusion or storage of mouse hearts is feasible and should provide an excellent model for the study of organ pretreatment with monoclonal antibodies or other agents prior to transplantation.