Traditionally, the mouse nonvascularized skin graft has been widely used in organ transplant research. There are, however, several limitations with this model, the main one being the different immune response of vascularized vs. nonvascularized grafts. We have recently developed a vascularized, orthotopic ear transplant model in mice. This model has several advantages that make it a useful tool to study many aspects of transplantation. The donor operation consists of harvesting the ear with intact arterial and venous pedicles. The arterial pedicle is dissected down to the common carotid artery with ligation of all branches except the auricular artery. The venous pedicle is based on the jugular vein with preservation of the auricular veins draining into the posterior facial vein. In the subsequent recipient operation, the graft is transplanted into an orthotopic position using the common carotid artery for arterial inflow and the jugular vein for venous outflow. We performed 16 such transplants (6 isografts, 5 allografts, and 5 xenografts), with a success rate of 94% (15/16). The donor operation time was 1.5 hours and the recipient operation time was 2.5 hours. The total time for anastamosis was 45 +/- 5 minutes. Serial biopsies were obtained on days 3, 5, and 7, and correlated with gross findings. In summary, this study illustrates that it is technically possible to transplant a mouse ear graft. The main advantage of this model is that it is a vascularized graft that can be visibly observed and easily biopsied, thus allowing for good correlation between gross and histological findings after transplantation. We plan to use this model further to study in detail the rejection patterns in an allograft and xenograft setting.