A single-institution pilot clinical trial was performed combining nonmyeloablative chemotherapy and the adoptive transfer of tumor-infiltrating lymphocytes with interleukin-2 in patients with metastatic melanoma. Nineteen patients were enrolled with 13 patients (68%) successfully completing treatment. An overall response rate (partial and complete responses) of 26% by intention to treat was achieved with a median follow-up time of 10 months. Of the 13 treated patients, there were 2 complete responses and 3 partial responses (38% response rate among treated patients), along with 4 patients with stable disease ranging from 2+ to 24+months. Three of the 4 patients with stable disease have had disease control without additional therapy, including one at 24+ months. Adoptive therapy with infiltrating lymphocytes is labor intensive but feasible and has a high response rate in treated patients.