Immunotherapy and biologic therapy of malignant melanoma are based on a sound scientific rationale and show promising preliminary results. As the nature of immune response to melanoma becomes further characterized, it is likely that more specific immune manipulations may be approached clinically. The fact that complete and partial remissions are induced in some patients with metastatic malignant melanoma by INF-alpha, IL-2, LAK cells, TIL cells, tumor vaccines, and the like clearly indicates a potential role for immunotherapy. As the overall response rates to these maneuvers are only in the range of 20%, more basic research is needed to understand more fully the immune mechanisms of tumor rejection. The combination of chemotherapy with biologic therapy has also provided promising leads. A major area waiting for development is the use of immunotherapy and biologic therapy as adjuvant treatment for the prevention of recurrence after surgical removal of high-risk Stage I/II and Stage III disease. The future of immunotherapy, either specific active immunization with appropriate vaccines or adoptive immunotherapy, must be based on well-defined molecules and antigenic systems, with appropriate enhancement based on the principles of immune reaction. Numerous strategies may be developed to enhance immune response, with resultant activation and proliferation of effector cells, including MHC- and non-MHC-restricted cytotoxic effector cells against tumor cells. The practice and principles of immunotherapy of human melanoma may be applied to other solid tumors that are resistant to chemotherapy and radiation therapy. Further experimentation in immunotherapy trials of melanoma may result in reliable and predictable clinical responses.