The accurate diagnosis of HPV-related diseases of the lower genital tract requires expertise, and sometimes even the expert may face a dilemma as to the precise nature of the biopsies submitted from colposcopically suspicious HPV-related lesions. We have evaluated the role of viral testing using dot blot hybridization (ViraType) and PCR in the diagnosis of histologically typical (42 cases) and equivocal (30 cases) squamous intraepithelial lesions of the vagina (7), vulva (30), perianal epithelium (3), penis (31), and scrotum (1). The viral kits were used according to the manufacturer's instructions in a routine laboratory setting, and the probes available were HPV 6/11, 16, 18, and 31, 33, 35 (the 30s group). HPV DNA was found in 45 of 72 (62%) of all lesions. PCR was more sensitive (58%) than ViraType (39%) for detecting HPV DNA sequences (p less than 0.02), particularly in equivocal lesions (EQHPV), 14 of 30 (47%) by PCR vs 4 of 30 (13%) by ViraType (p less than 0.004). The majority of lesions contained oncogenic type viruses irrespective of their histologic presentation, namely, type 16. Only condylomata acuminata were predominantly HPV 6 or 11 positive. Viral testing may play a role in the quality control of the diagnostic expertise of routine laboratories as well as ascertaining the HPV-relatedness of histologically equivocal lesions of the anogenital tract. In view of the relatively high false-negative rates for detecting HPV DNA by ViraType and PCR, only a positive test may be meaningful unless other HPV types are added.