The clinical regression of cottontail rabbit papillomavirus-induced cutaneous papillomas on Dutch-belted rabbits following treatment with hematoporphyrin derivative photodynamic therapy was recently reported. Those papillomas that underwent total regression failed to recur at 18 months. Tissues from totally regressed papillomas and adjacent sites failed to reveal the presence of papilloma on histological examination. These findings were confirmed by the absence of viral DNA following analysis by Southern blots for cottontail rabbit papillomavirus viral copy number and DNA restriction pattern. Partially regressed papillomas and untreated papillomas revealed histologically typical papillary features with approximately equal amounts of viral DNA.