DESCRIPTION: (Applicant's Abstract) The applicant's long term goal is to develop an effective vaccine to treat malignant melanoma. As part of this process, he has completed preclinical studies that show a potent way of increasing the effectiveness of his melanoma vaccine is to use QS-21, a novel adjuvant. He wishes to take advantage of this new development in the laboratory to investigate whether QS-21 will improve the potency and clinical effectiveness of an existing melanoma vaccine which has shown promising results in clinical trials. Specific aims are: 1) To conduct a Phase II clinical trial, to determine whether the immunogenicity of a polyvalent melanoma antigen vaccine can be increased by admixing the vaccine with QS-21. Thirty-two patients with AJCC stage IV (disseminated disease) melanoma will be randomized to treatment with melanoma vaccine admixed with a standard adjuvant (alum) or with one of three different dose levels of QS-21 (25ug, 50ug, or 75ug/immunization site). On two occasions prior to, and at fixed intervals following vaccine immunization, antimelanoma B and T cell responses in the different groups of patients will be compared. Multiple parameters of the humoral and cellular immune responses will be measured since QS-21 may affect these differently and the mechanism of action of this adjuvant needs to be elucidated; 2) Determine the optimal biological dose of QS-21 that maximally potentiates each of these responses; 3) Evaluate the toxicity, and; 4) The clinical effectiveness of this treatment.