A patient with metastatic melanoma who had progressive disease after prior surgical resections, high dose interleukin-2, and anti-cytotoxic T lymphocyte antigen-4 antibody received sequential treatments with autologous tumor infiltrating lymphocytes that recognized the gp100 melanocyte differentiation antigen. Although no clinical response was seen when cells were administered alone, an objective clinical response to therapy was seen with tumor infiltrating lymphocytes administered together with a highly immunogenic fowlpox vaccine expressing a gp100: 209-217 (210M) epitope. Persistence of the transferred antigen-specific lymphocytes in the peripheral blood was observed only after adoptive cell therapy plus administration of vaccine. Cell proliferation in vitro was further stimulated by additional vaccine and interleukin-2. The patient has an ongoing partial response at 10 months after the last treatment.