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Antimelanoma antibodies previously demonstrated in the serum of melanoma patients by immunofluorescence have now been detected by a sensitive and quantitative complement fixation technique. The melanoma-specific antibodies detected by both of these techniques show a remarkable correlation with the stage of disease. Study of serums from 63 melanoma patients showed that both the incidence and titer of antibodies to the tumor antigens of malignant melanoma were found to be higher in patients with localized melanoma than in those with widespread metastatic disease. Furthermore, study of serial serum specimens on melanoma patients revealed a drop in antibody titer to undetectable levels with advancing metastatic disease. Additional evidence for the importance of immunological factors in this disease came from studies of delayed cutaneous hypersensitivity in melanoma patients. All patients with localized melanoma were capable of being sensitized to DNCB, whereas all patients who could not manifest delayed cutaneous hypersensitivity to this chemical had widespread metastatic disease. Eight melanoma patients were treated with immunotherapy using BCG as an immunological adjuvant. This therapy produced a rising titer of antimelanoma antibody and temporary tumor regression in five patients. However, only one of these patients has had a complete regression and remains free of disease at two years following treatment. There was a good correlation between the patient's immunological competence and his response to immunotherapy. All patients who could be sensitized to DNCB or tuberculin and developed a fourfold rise in antibody titer had some response to immunotherapy, whereas anergic patients failed to respond to this therapy. These studies indicate that the host immune response to malignant melanoma is an important factor in controlling the progression of this disease. Therefore, immunotherapy may become a useful adjunct to the primary surgical therapy of malignant melanoma.