Human papilloma virus (HPV) has been demonstrated in a series of benign proliferative lesions of skin and mucosae. To prove the distribution of HPV in the oral proliferative lesions at the ultrastructural level, we performed electron microscopic analysis of 10 specimens taken from 5 patients through large excisional biopsy. All of them were diagnosed pathologically as fibropapilloma. In each patient, specimens were taken from both clinically evident proliferative lesions and clinically normal surrounding mucosa. Obtained specimens were fixed in a glutaraldehyde solution and processed for routine ultrathin sectioning. Before electron microscopic observation, the tissue sections on copper grids were subjected to amylase digestion of glycogen granules. Spherical viral particles of 40-55 nm in diameter were detected the non-keratinized epithelial cells in all specimens examined. Of particular interest were the large amounts of viral particles found in the cytoplasmic matrix and nuclei (especially on their chromatin masses) of the cells in intermediate and surface layers, which did not form a crystal array. All the membranous cell organelles of epithelial cells were, however, devoid of viral particles. Some viral particles were distributed in the extracellular spaces of an intermediate layer. Viral particles were hardly observed in the cells of a basal/suprabasal and prickle cell layers. There were no significant differences in the HPV distribution between the cells derived from the proliferative lesion and those derived from the surrounding normal mucosa.