Since 1975, Phase I and II studies have demonstrated the successfulness of hematoporphyrin derivative photodynamic therapy in the treatment of various malignancies of the skin, eye, bladder, lung, and head and neck. Moreover, two cases of traditional Western cutaneous Kaposi's sarcoma (TKS) have been treated with photodynamic therapy with both early and late complete response. To date, attempts at cure and palliation of the more aggressive AIDS-related oral Kaposi's sarcoma with conventional radiation, chemotherapy or immunotherapy, or surgical excision have been limited and often associated with debilitating mucositis and further immunosuppression. Certain aspects of photodynamic therapy may be efficacious for treatment of Kaposi's sarcoma: (1) the selective retention of hematoporphyrin derivative by neoplastic lesions; (2) a tumor-specific cytotoxic agent (i.e., free oxygen radical); (3) absence of systemic toxicity from immunosuppression; and (4) the potential for retreatment without increasing side effects. Herein we present five cases of AIDS-related KS (EKS) with diffuse, superficial, and nodular oral lesions treated with dihematoporphyrin derivative and photodynamic therapy with subsequent dramatic early partial and complete responses.