Hematoporphyrin derivative has been shown to selectively localize in malignant tissues and chemically induced animal papillomas. It is a powerful photo-sensitizing agent that can cause destruction and death of tissues in which it has localized by the generation of singlet oxygen when activated by light of the appropriate wavelength (photodynamic therapy [PDT]). Laryngeal papillomas are rapidly growing benign epithelial neoplasms with a clinical course marked by multiple recurrences after surgical removal. Before considering PDT as a therapeutic modality in the treatment of this debilitating disease we developed an animal model for experimentation. Using the cottontail rabbit papillomavirus, sometimes referred to as the Shope papillomavirus, large cutaneous papillomas were induced on the backs of Dutch Belted rabbits. Following intravenous administration of hematoporphyrin derivative, PDT was delivered with white light. Marked regression of the papillomas was noted with replacement by normal hair-bearing skin. The clinical implications of this work to the control of laryngeal papillomatosis is discussed.