The identification of proteins and carbohydrates associated with melanoma led to development of defined antigen vaccines. However, vaccines derived from whole allogeneic cells have a number of advantages. Melacine is an allogeneic melanoma tumor cell lysate combined with an immunologic adjuvant, DETOX. Phase I and II trials in stage IV melanoma showed low-level antitumor activity, but this vaccine has its greatest promise in the adjuvant setting. A phase III trial indicated a survival benefit for Melacine in the subset of melanoma patients who express the HLA class I antigens A2 and/or HLA-C3. This finding must now be prospectively confirmed.