A 30-year-old man with bilateral plantar warts of the mosaic type which had been resistant to standard treatment modalities was treated with diphenylcyclopropenone. After 10 weeks, the treated warts had disappeared; the untreated warts, although showing some involution, still persisted. The untreated warts, serving as a control to prove the effectiveness of topical immunotherapy, responded likewise to subsequent treatment with diphenylcyclopropenone. Wart regression was reflected histopathologically by decreases in acanthosis, papillomatosis, granular vacuolation, and hyperkeratosis. Immunohistochemically, Ki-67 expression was markedly reduced, and a reversal of the CD4/CD8 ratio was seen. These findings suggest a major role of a cell-mediated immune response in the spontaneous resolution of warts.