Since it is well established that cellular immunity plays a role in the defense against melanoma, the morphologic aspects of this reaction warranted investigation. Accordingly, peripheral blood mononuclear cells obtained from healthy donors were incubated with human melanoma cells for 1 to 24 hours to examine, on the ultrastructural level, the cellular interaction that eventuates in cytolysis of the tumor cells. Within 1 hour of incubation, monocytes and lymphocytes were seen attached to approximately 40 per cent of the melanoma cells with marked interdigitation of cellular processes. After 4 hours of incubation, the percentage of tumor cells with attached leukocytes remained the same, but 2 to 9 per cent of the melanoma cells showed interiorized lymphocytes when kept in suspension, 10 to 25 per cent when maintained in culture dishes. Erythrocytes or fixed lymphocytes were not taken up by the melanoma cells nor were living lymphocytes seen in fibroblasts or endothelial cells which served as controls for the neoplastic cell lines. Thus, melanoma cells did not prove to be randomly phagocytic, and the interiorization displayed by lymphocytes--a process called emperipolesis--appears to be selective. It is postulated that emperipolesis may enhance the tumoricidal effect exerted by cytotoxic lymphocytes on melanoma cells.