Human papillomaviruses (HPVs) have been identified in benign and cancerous epithelial lesions of the female genital tract. They have also been identified in papillomata and cancers of the upper aerodigestive tract. This study investigates the hypothesis that lesions of the cervicovaginal area are more common in women with cancers of the head and neck region. The presence of HPV in lesions of both regions is examined. Seven female patients with cancer of the upper aerodigestive tract had DNA analysis of their carcinoma specimens. HPV type 16 was found in two of the seven (28%). Fourteen female patients with upper aerodigestive tract cancers had Papanicolaou smears to search for cytologic evidence of HPV infection, and cervicovaginal lavages to analyze DNA from exfoliated cervical cells. Five of thirteen (38%) Papanicolaou smears revealed koilocytotic atypia and three of these patients had HPV DNA types 16 or 18 identified in the cervical lavage. The incidence of cervical atypia noted is 13-fold greater than average. One patient had HPV type 16 in both her supraglottic cancer and in her cervicovaginal lavage. Evidence of HPV infection at two separate anatomic sites suggests a systemic susceptibility to HPV infection.