Human papilloma virus (HPV)–related cutaneous manifestations occur with increased frequency and severity among HIV-infected persons. In this report, we describe an HIV-infected man with persistent, severe cutaneous hand warts that did not respond to multiple therapies, including liquid nitrogen cryotherapy, topical dinitrochlorobenzene, topical podophyllin, and intralesional interferon-alfa injections. Approximately 1 year after starting a potent protease inhibitor–containing antiretroviral regimen, the patient’s recalcitrant cutaneous warts markedly diminished in size, even though the patient did not receive any specific therapy for the warts after starting aggressive antiretroviral therapy. The patient continued on a potent protease inhibitor–containing antiretroviral regimen and, approximately 2 years later, the warts completely resolved. Our patient’s dramatic clinical improvement of cutaneous HPV infection that followed protease inhibitor–containing antiretroviral therapy provides a clear-cut example that protease inhibitor–containing combination antiretroviral therapy can produce significant clinical benefit. (J Am Acad Dermatol 1999;40:818-21.)