The expression of immune associated surface antigens of keratinocytes was studied in human papillomavirus (HPV) derived lesions in order to determine whether HPV types have a regulatory role in the pathogenesis of papillomas. A series of cutaneous and mucosal lesions were immunolabeled with monoclonal antibodies to the major histocompatibility complex class 1 (beta 2-microglobulin) and 2 (HLA-DR antigens), intercellular adhesion molecule (ICAM-1) and glycoprotein CD36 (OKM5) as well as CD1a (Langerhans cells), CD4, CD8 (T cells) and CD11a (LFA1 antigen). Testing for the presence of HPV was carried out by in situ hybridization with biotinylated probes for viral DNA detection and typing. We observed a drastic reduction or a loss of beta 2-microglobulin by keratinocytes from cutaneous lesions in correlation with the disappearance of Langerhans cells. Only mild alterations were observed in mucosal lesions. HLA-DR expressed by keratinocytes was only detected in condylomas and laryngeal papillomas and was usually associated with a dense inflammatory reaction. This HLA-DR expression may be correlated with an up-regulation of ICAM-1 and the presence of LFA1 positive leukocytes, mainly of CD8 phenotype, in the epithelium. CD36 was detected on differentiated keratinocytes of all lesions; its expression seems related to the proliferation state of the lesions and probably does not represent an immune marker. The different reactivity patterns observed in cutaneous and mucosal lesions may reflect: 1. different roles for mucosal and cutaneous HPV types in the induction of immunoregulatory surface antigens of keratinocytes, or 2. the changing nature of the cytokines released by mononuclear cells and infected keratinocytes in these lesions.