A series of 191 oral mucosal tumors including those with suspected HPV (Human Papilloma Virus) etiology; squamous cell papilloma (SQP), condyloma acuminatum (CA), focal epithelial hyperplasia (FEH), as well as those regarded as unrelated to HPV; fibrous hyperplasia (FH), papillary hyperplasia (PH), and true fibroma (TF), were analyzed for HPV structural proteins (by indirect immunoperoxidase IP-PAP technique), for the presence of epithelial dysplasia, and for the cellular composition (B and T lymphocytes, mononuclear phagocytes, (MPS cells] of their local inflammatory cell infiltrates using ANAE-(acid alpha-naphthyl acetate esterase) stain. HPV structural proteins were disclosed in 85% of FEH, in 75% of CA, and in 41% of SQP. These three lesions significantly differed from PH and FH with regard to the intensity and cellular composition of the local infiltrates, being most intense and B cell predominated in the latter two. Mild dysplasia was found in 20% of both CA and SQP lesions, the former also showing moderate dysplasia in 12% of cases. The HPV antigen positivity was negatively correlated with dysplasia in CA and SQP, the intensity of the infiltrate showing positive association with dysplasia. The results are discussed in terms of HPV etiology of CA, SQP and FEH, of the host immunologic reactivity against these lesions, as well as of the possible role of HPV in human squamous cell carcinogenesis.