We performed an immunohistochemical analysis of skin biopsies from 13 allogeneic bone marrow transplant (BMT) recipients, undergoing either acute graft-versus-host-disease (aGVHD, n = 8) or chronic GVHD (cGVHD, n = 5). A panel of different monoclonal antibodies (MoAb) was employed including anti-CD2, -CD3, -CD4, -CD8, -CD11b, -CD16, -CD56, and -CD57, as well as a recently described reagent (HP-3B1) specific for a novel natural killer (NK)-associated cell-surface antigen (Kp43). Our data indicate that in aGVHD lesions the proportions of CD2+ cells often exceeded those detected with anti-CD3 MoAb. Double labeling confirmed the presence of CD2+ CD3- lymphocytes and suggested the coexpression in some cells of CD2 and CD11b. When MoAb specific for non-lineage-restricted NK-associated markers were employed, anti-CD56 and -CD57 occasionally stained variable numbers of lymphocytes (means = 14.6% of mononuclear cells in 0.05 mm2, range less than 1-48% and means = 10.3%, range 2-25%, respectively), whereas no CD16+ lymphocytes were observed. In contrast, most samples consistently displayed substantial proportions of Kp43+ cells (means = 32.8%, range 12-63%), which appeared CD3- and were mainly located at the dermoepidermal junction. On the other hand, sections from most (four of five) cGVHD lichenoid lesions analyzed displayed lower proportions of Kp43+ and CD56+ cells. Our data point out the interest of the anti-Kp43 MoAb to identify NK cells in aGVHD lesions, suggesting their pathogenetic participation.