Malignant melanoma is resistant, except for a small percent, to treatments such as radio and chemotherapy. On the other hand melanoma has been considered as the prototypical immunogenic tumor in which the immune system may have a role in the outcome of the disease. Immune cells from cancer patients respond poorly to mitogenic or antigenic stimuli. One reason for this is the rapid turn over of the T lymphocytes arising from the apoptosis of these cells. The induction of apoptosis in the activated T lymphocytes is considered as one of the ways the tumor cells avoid recognition and destruction. The Fas (APO-1, CD95)/FasL pathway is well know to induce apoptotic celi death in many cells. In this study the expression of Fas and its correlation with apoptosis on CD4+ and CD8+ T cells in PBMCs from melanoma patients was measured. Annexin V was used to measure apoptosis. For the present study, we obtained 5ml of venous blood from 16 pa-tients and 10 healthy controls. The lymphocytes were then isolated using the Ficoll-Hypaque gradient centrifugation. The lymphocytes were then incubated in medium for 24hrs and then stained with PerCP-labled monoclonal antibodies of anti CD4 or anti CD8. They were then washed and stained with PE labeled CD95 antibody. The cells were then washed and stained with Annexin V FITC. The cells were then measured using a three color flow cytometer. The correlation between the CD4+ Annexin V+ and CD4+ Fas+ Annexin V+ for patients was r=0.84 and for controls was r=0.81. For CD8+ a similar result was obtained with CD8+ Annexin V+ and CD4+ Annexin V+ Fas+ was r=0.82 for patients and r=0.78 for controls. The Fas/FasL pathway may not be the only mechanism responsible for the increased apoptosis of CD4+ and CD8+ cells but the contribution is significant.