Studies of the regional nodes (RLN) of melanoma patients, using immunohistology with anti-S-100 protein and monoclonal antibodies have shown occult tumor cells (OTC) in nodes ostensibly tumor-free by H&E staining. OTC were demonstrated in 14% of Stage I patients, mainly those with deep, thick primaries and 30% of Stage II patients, mainly those with at least 3 tumor-positive nodes on H&E. The nodes containing OTC are those nearest to tumor on the direct lymphatic pathway (dye studies). Parallel studies show nodes in the same position to be immune suppressed (histology, immunohistology, response to mitogens, alloantigens and lymphokines) and to contain many suppressor T cells (Con-A). Melanoma-derived materials (gangliosides, prostaglandins, lipoprotein antigens) downregulate lymphocyte and macrophage functions, providing a possible mechanism for the suppressed function of nodes near tumor, a suppression that may facilitate tumor cells as evidenced by the survival of OTC.