The use of photodynamic dye and light inactivation for the treatment of genital herpes simplex virus infections is associated with the risk of potential oncogenesis. Patients (16) treated with neutral red and fluorescent light for documented herpetic infections were studied at intervals from 9-52 mo. following treatment. Four patients treated with other modalities were included in the study. Biopsies of the treated areas were obtained, and 3925 tissue sections were examined. Mild atypical epithelial changes were focally present in most specimens regardless of therapy. Histologically identifiable premalignant change could not be demonstrated.