We studied how frequently patients with malignant melanoma have specific antibody to cell surface antigens of cultured autologous melanoma cells as demonstrated by mixed hemadsorption assays. Of 35 patients studied over periods ranging from 1 to 36 months with Stage II, III, and IV disease, two showed consistent and high titered reactivity against autologous melanoma cells, two showed less consistent and intermediate reactivity, seven showed sporatic, low titered reactivity, and the remainder were consistently negative. A detailed analysis was carried out with the sera of one patient with sufficiently high titer against autologous melanoma cells. By direct tests and by absorption analysis with a variety of melanoma and nonmelanoma cell lines which included autologous fibroblasts, the antigen could not be demonstrated on any cell type other than the autologous melanoma.