Seventy-three patients with vulvar intraepithelial neoplasia (VIN) grade III were followed for a median of 5 years after primary treatment. Thirty women also had a diagnosis of cervical neoplasia. During the follow-up 26 patients (36%) had one or more vulvar recurrences. Recurrences were seen significantly more often in the patients who also had cervical neoplasia, indicating a common etiology. Microinvasive carcinoma developed in 12 patients, 3 of whom later developed frankly invasive vulvar cancer. The original, paraffin-embedded vulvar specimens were examined by the polymerase chain reaction for human papillomavirus DNA of the types HPV 6, 11, 16, 18, and 33. HPV types 16 and 33 were found in 90% of the VIN lesions. It is concluded that VIN III is an HPV-related disease in all or almost all cases, and that a generalized genital HPV infection may be a factor in the development of multicentric genital neoplasia. No association was observed between the specific HPV type and the risk of recurrent vulvar disease, cervical neoplasia, or malignant progression.