Xenotransplantation, with organs harvested from appropriate donor animals could be a potential solution to the shortage of donor organs in general and of lung grafts in particular. Unilateral orthotopic lung transplantation in the rat has been used to study the lung xenograft rejection in a discordant donor-recipient combination, i.e. guinea-pig to rat. With this microsurgical technique, a high post-operative survival rate has been reached. The good function of the grafts was assessed by serial chest x-ray, lung perfusion scintigraphy until several months after the transplantation. The survival of the xenografts has been then compared to that of allografts and isografts. Lung xenograft rejection in this combination has been very fast: 53 minutes. Macroscopic and histologic data displayed lung infarct with hemorrhagic edema.