Human graft-versus-host disease (GVHD) has several cutaneous manifestations, including a lichenoid and a sclerotic injury pattern. A versatile animal model of graft-versus-host skin disease (GVHSD) would facilitate study of the pathophysiology of these two cutaneous injury patterns. We have examined two murine chimeras histologically and have found two distinct patterns. Allogeneically transplanted B1/6 mice show a prolonged lichenoid-interface dermatitis that eventuates in clinical alopecia, whereas LP/J recipients of allogeneic cells do not show hair loss. Their histopathology consists of an early lichenoid phase that abates and is replaced by dermal sclerosis. Because of the versatility of the mouse as a laboratory animal, we feel that this model provides an excellent opportunity to define the immunopathologic mechanisms responsible for skin injury in GVHD. In addition, an understanding of the pathogenesis of the T cell-dependent, lichenoid, and sclerotic patterns of tissue injury in GVHSD might well provide insight into the pathogenesis of the GVHSD analogs, cutaneous lupus erythematosus and scleroderma.