Vaccination of Melanoma Patients With Total or CD25-depleted Peripheral Blood Mononuclear Cell (PBMC)

Inclusion Criteria: * Patients must have histologically or cytologically confirmed malignant melanoma that is unresectable stage III or stage IV. Measurable disease is not required. * Patients must have failed, refused, or not been eligible to receive at least one standard therapy regimen for metastatic disease. * Easily harvested metastatic tumor cells e.g., skin or lymph node metastases or a planned surgery to remove tumor. Patients undergoing resection of a solitary brain metastasis are eligible if their resected lesion contains an adequate number of tumor cells. A minimum 2 cm x 2 cm x 2 cm lesion will be required for study eligibility. * Sufficient viable tumor cells harvested to generate the vaccine. The tumor collected must contain greater than 1.6 x 108 viable tumor cells or a cell line generated from autologous tumor must provide greater than 1.6 x 108 viable tumor cells. * Patients may have received prior chemotherapy and/or immunotherapy. Prior radiation therapy is acceptable but previously radiated sites may not be used for tumor collection for vaccine preparation. * Life expectancy of greater than or = 3 months. * ECOG performance status \<2 (Karnofsky \>60%; see Appendix A). * Patients must have normal organ and marrow function at the time of enrollment as defined in the protocol. * Patients must be seronegative for HIV, Hepatitis B surface antigen and Hepatitis C antibody. * If patients have had recent surgery, they must have recovered from the effects of that surgery in the opinion of the investigator. * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * Patients who have had chemotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C). * Radiation therapy within 2 weeks. Prior radiation must have been to less 30% of the bone marrow and patient has recovered from all side effects, in the opinion of the investigator. * Patients may not be receiving any other investigational agents. * Steroid therapy, other than replacement steroids and inhaled steroids. Patients who might require systemic corticosteroids other than replacement steroids during the next three months are not eligible for this study. * Patients with known brain metastases unless treated with radiation therapy and/or surgery and shown to be stable \> 1 month. * Autoimmune disease requiring treatment, with the exception of controlled autoimmune thyroiditis or vitiligo. * Pregnant or nursing women are excluded from this study because fludarabine and cyclophosphamide have potential teratogenic effects. It is not known whether fludarabine is excreted in breast milk but the package insert cautions that it might and recommends against breastfeeding if the mother is treated with fludarabine. * Uncontrolled intercurrent illness which, in the opinion of the investigator, may increase the risks associated with study participation or interfere with the interpretation of the results.. * Any other medical illness or psychiatric condition/social situations that in the opinion of the principal investigator would compromise the patients ability to tolerate this treatment or would limit compliance with study requirements.