In addition to their role in hemostasis and thrombosis, platelets are important modulators of immune and inflammatory responses. We provide evidence here that human platelets contain abundant quantities of Fas-L, and upon activation, they express it on their surface as well as release it into medium. This surface-expressed Fas-L is biologically active and can induce apoptosis in Fas-positive human tumor cells. Therefore, activated platelets may represent an important player in Fas/Fas-L-mediated apoptosis.