A composite tissue comprises tissues derived from all three germ layers: ectoderm, mesoderm, and endoderm. Following transplantation, each component induces an immune response, which differs in character and intensity. Skin has been shown to be the most antigenic tissue and is the first tissue to be rejected in animal models and human transplants. The heightened antigenicity of skin has been attributed to Langerhans' dendritic cells and skin-specific antigens. Muscle, bone, cartilage, and nerve predictably induce a relatively lower immune response in that order. However, rejection of even one component of a composite tissue renders the entire allograft vulnerable to dysfunction. The knowledge of relative antigenicity can lead to the development of strategies intended to decrease the antigenicity of a specific component. In addition, a better understanding of this relative antigenicity of allograft components enables the concept of tailored immunosuppression targeting only specific cellular and humoral components of rejection. This would limit the amount of immunosuppression used and the consequent related complications of opportunistic infections and malignancies.