We tested grade III cervical intra-epithelial neoplasms (CIN III), genital invasive carcinomas and healthy genital tissues for the presence of a number of viral and cellular parameters, considered to be risk factors in genital oncogenesis. The results show that: (I) about 30% of genital tumors had homology to HSV-2 BglII N and/or BamHI E DNA fragments; (2) positivity to HSV-2-specific protein ICP10, encoded by sequences within the HSV-2 BamHI E DNA fragment, was detected in 29/55 neoplastic genital tissues but not in healthy genital tissues or tumors at other sites; (3) HPV-16 DNA was found in about 50% of tumor samples, but none of the positive tissues reacted to HPV capsid protein or to the protein encoded by the HPV-16 E6 ORF; (4) 6/8 tumor samples showing homology to HSV-2 DNA fragments also hybridized to HPV-16 DNA; (5) c-myc amplification was not detected in any of the analyzed samples, but tissues from 4 patients were positive for c-myc expression. None of the considered factors was present in all the analyzed samples; nevertheless, some tissues showed the simultaneous involvement of several parameters, suggesting that a number of risk factors may be involved in different steps of human genital oncogenesis.