An outbreak of a new form of oral leucoplakia, found principally on the lateral borders of the tongue, is reported in male homosexuals in the San Francisco area. Many of the patients showed evidence of immunosuppression, and candida was often found in the lesions. The characteristic histology is similar to that of the flat wart of skin. There was immunocytochemical evidence of papillomavirus core antigen in 77% of 30 biopsy specimens, but no papillomaviruses were detected by electron microscopy in samples from 6 randomly selected patients. In 5 of these 6 patients there was evidence of a herpes-type virus. Pneumocystis carinii pneumonia has developed in 8 of 37 patients in a 33-month period. This leucoplakia may presage AIDS, may be associated with both papillomavirus and a herpes-type virus, and may offer clues to the pathogenesis of other forms of oral epithelial hyperplasia and dysplasia.