Malignant melanoma accounts for most of the increasing mortality from skin cancer. Melanoma cells were found to express Fas (also called Apo-1 or CD95) ligand (Fast). In metastatic lesions, Fas-expressing T cell infiltrates were proximal to FasL(+) tumor cells. In vitro, apoptosis of Fas-sensitive target cells occurred upon incubation with melanoma tumor cells; and in vivo, injection of FasL(+) mouse melanoma cells in mice led to rapid tumor formation. In contrast, tumorigenesis was delayed in Fas-deficient lpr mutant mice in which immune effector Cells cannot be killed by Fast. Thus, Fast may contribute to the immune privilege of tumors.